Puberty is not only an awkward age, it's also an age full of heartbreak.
- Jessi crying to her mom that she got her first period on her school trip (after her mom made her wear white shorts). While her Inelegant Blubbering is played somewhat as a joke, her all-too-familiar feeling of humiliation is definitely not.
- Jay snapping at his older brothers after they ruin his sleepover, who continue to casually bully him until he runs off in tears. It's the first time we see Jay's more humble side and realize exactly why he can be so insufferable.
- Jessi receiving unwanted attention after wearing a new bra under a tank top to school. A particularly uncomfortable compliment from Mr. Lizer and Lola snapping her bra strap sends her running into the bathroom in tears.
- When talking to Ms. Benitez, Coach Steve reveals that no one has ever asked him "Are you okay?". That is a very sad thought, that no one before her had ever been concerned for him to even ask that.
- Jay has cameras in Nick's house, but this time it's not because he's a massive perv. He just likes watching Nick's mom cook because his own mom is an abusive monster whose idea of making dinner is shredding open a bag of McDonald's and making the boys duke it out.
- Jessi is angered when Nick tells her that her mom is cheating on her dad with a woman; and then he says he knows this because he and Andrew saw her do it while they were in the city. She gets even angrier because that trip was two weeks ago, and they said nothing. She storms off after calling Nick a bad friend.
- "I Survived Jessi's Bat Mitzvah":
- Andrew and Missy breaking up at Jessi's bat mitzvah. Afterwards, even Maurice is heartbroken and the two cry in each other's arms as Amason's cover of "I Wanna Know What Love Is" plays the episode out.
- Jessi's flashbacks of her parents' marriage. It progresses from starting out very happy and affectionate when she was a baby, to showing signs of falling apart when she's a little kid, to the present day where it is now visibly unhappy and strained. The saddest part is that both of them clearly love her, but their own relationship makes it hard for them to show it.
- Jessi tells Jay that her dad hired his dad to be his divorce lawyer. She also mentions that her dad now has to sleep in the basement and shower using the backyard hose.
- Missy hits a new low in self esteem and wears a hoodie to school, desperate to hide what she considers to be her shameful, ugly body. Her reflection also constantly shows up reminding her to hate herself.
- Jessie's body-positive self esteem, which was just bolstered after the song number, is deflated when she runs into Cantor Dina at the spa and is furious to find that of all women, the one she had nothing but contempt for has a flawless naked figure. She hates Dina so much that she's resentful of something that's literally nobody's fault.
- Greg breaking down in front of Jessi, tearfully confessing that he still loves Shannon and is well-aware of his own failures as a husband.
- Lola's home life is terrible. Her condo is staged because her mom wants to sell it as soon as possible, and her mom apparently wishes that Devin was her daughter, not Lola.
- After Andrew says that he wants to break up with her, Lola expresses just how lonely she is.Lola: You're like weak and boring and, like, a nobody! What does it mean that even you don't wanna be with me?
- Greg is kicked out of the house because Jessi found and ate one of his edibles. Even worse, the Shame Wizard finally takes control over her and makes her feel even worse about breaking up the otherwise beautiful relationship of her parents and even finds a way for her to blame herself for Trump's election.
- Gina being slut-shamed and harassed for her developing body. It comes to a head in "Dark Side of the Boob" when word leaks out that Nick touched one of her boobs, and it utterly ruins their relationship.
- Missy locks herself in the bathroom to cry after her classmates catch her dry-humping her worm plushie.
- Matthew discovering that even though his classmates seem accepting of him, they still view him as an outsider. Devin emasculates him by saying he isn't a 'real boy' and the other boys get in his face and tell him not to rape them. It quickly becomes apparent that his bitchy attitude is nothing but a defense mechanism and his only choices are keeping his guard up or getting bullied. The Shame Wizard eventually finds him sitting in a fetal position on his sleeping bag, calling him a 'lonely little queer'. Sadly Truth in Television for plenty of young gay people like Matthew.
- While getting jealous of Andrew and Missy, Lola notes that the condo she lives in is under her name, likely because her mom doesn't want to own the place where Lola lives.
- Even though the Shame Wizard is gone and everyone else is partying, Jessi is unhappy and tells Connie to get out of her life.
- Connie is in tears after Jessi states that she wants to go with Depression Kitty.
- Andrew sees that the Shame Wizard has no friends among the other monsters.
- The once tightly-knit gang that started out the series planning to go to the school dance together spend less and less time with each other. By the finale, they've all gone their separate ways.
- Missy cries when the girls call her a traitor for not dressing up in skimpy clothing like they are.
- While Nick has his face buried in his phone, his mother tearfully informs him that his maternal grandmother is dying of cancer, but also suffers from Alzheimer's so even if someone tells her she's dying, she won't remember it. He's too distracted to care.
- Jay is left to fend for himself after his family leaves for spring break and their house is fumigated. Luckily, the Birches let him stay with them, even after the Bilzerians come back.
- After leaving the Bilzerian household and making a new home in the Birch's attic, Featuring Ludacris says: "I'm afraid that if I can't be happy here, then perhaps I'm the problem."
- Ali telling Jay the real reason she had to change schools. It wasn't because she fingered a nun, as has been the rumor, but something far more grounded in reality: she told her best friend she was in love with her and her friend, in return, told everyone at school that Ali was a "lezbo."
- In the same episode, while Jay doesn't come out in the most tactful way, he still shares a personal detail about himself that he's proud of himself for discovering, having been inspired by Ali's own self-confidence. However, his friend, including Matthew, who should know better, outright tell Jay that bisexuality doesn't exist and he's just in denial, largely thanks to Ali's misinformation. It's something plenty of real bisexual people have had to deal with.
- Nick, Andrew and Jessi sitting alone while everyone else dances at the Devons' faux-wedding.
- Because of the pressure Shannon puts on her and the consequences of her parents' divorce, Depression Kitty begins to stalk Jessi once again, to the point where Jessi refuses to get out of bed the morning of her exam and do nothing. Sadly Truth in Television: depression isn't like the flu or a cold, it's more like a chronic illness which can be tolerable some days and insufferable others.
- "Super Mouth" has several, emphasizing the depressing nature of change:
"Now we've got problems / And I don't think we can solve 'em / You made a really deep cut / And baby now we've got bad blood."
- Andrew is crestfallen when he finds out that Missy is falling for Nick. Their friendship is shaken and they get into a big fight that leads to Andrew dropping out of summer camp just because he wants time away from Nick. And then Nick breaks Missy's heart by being forced to admit that he doesn't love her back. A lifelong friendship was broken over nothing.
- Jessie discovers that her superpower is getting people to reveal secrets when she touches them. Unfortunately, they're all secrets that have been kept from her, like how her father is dating another woman and her mother is moving them to the city against her will, or things she doesn't want to hear, like how Matthew is going to be too busy with his boyfriend to miss her when she leaves.
- The Reveal that the entire "superhero" plot of the episode was just a metaphor for how chaotic the group's relationships have become, as realized by Caleb's drawings. It perfectly captures how interpersonal drama feels for those going through it verses those merely observing it: to the observer, a bunch of kids bickering in the rain is utterly pathetic. To the kids going through it, it's literally the end of the world.
- People being insensitive and cruel to Natalie, just because she's transgender.
- Nick throughout this season. This poor guy needs a hug.
- First, he faces some downright cruel humiliation from Andrew and the other kids at his camp, as Andrew is still mad about him and Missy throughout the first three episodes.
- Then, just when things seem to get better for him after reconciling with Andrew, he has a nightmare where he is alone and friendless, in a Crapsack World Bad Future.
- This make him realize his feeling towards Jessi, which he then attempted to act on, to no avail.
- He then develops a fear of intimacy as a result of everything he's been through, thinking that letting people close to him will just hurt him.
- Finally, he has an out of body experience, and has his future self taking over his body as a result of his fears and self-loathing overpowering him.
- Missy arguing with her parents after changing her hairstyle, ending with her tearfully going to her room and saying she just wanted to show them her hair.
- Natalie has her first kiss with Seth, but he's embarrassed because she's trans, which understandably hurts her feelings pretty badly.
- Jessi being plagued by the Depression Kitty and the Anxiety Mosquito as she struggles to cope in the city.
- The Code-Switchin' song, while humorous at times, can be pretty depressing for those who are African-American, as they feel pressured to "Code-Switch" in order to appeal to another race, or even those of their own race.
- Coach Steve crying about what happened to the Twin Towers on his birthday, September 11, declaring that he never wants to celebrate his birthday again. His manchild antics are usually Played for Laughs, but in this case it makes his shock and sadness more painful. It's enough to make Matthew sympathize with Steve after taking advantage of his stupidity all episode.
- Nick and Connie part on bad terms after Connie decides to stop being Nick's Hormone Monstress.
- Jay is desperate enough for physical affection from his family that he welcomes Kurt punching him."Worth it. Physical touch.. means you love me."
- After Michael Angelo dumps her and Shannon finds out that she's been skipping school, Jessi can only hide under her sheets and cry herself to sleep.
- Matthew's mother finds out he's gay and alienates him on the spot. While his father ends up accepting him as is, the last we see of Matthew for the season is him sitting alone on a swing set during Connies verse in What You Gonna Do?
- Despite a very strong and fairly healthy relationship, Lola and Jay's relationship ends badly after Lola can't bring herself to return Jay's "I love you" because of how hurt she's been by other people in her life, which leads to Jay cheating on her with two of his pillows.
- "My Furry Valentine":
- Andrew's increasingly douchey behaviour is hard to watch. He goes from trying to win back Missy with confidence to trying to win her back with desperation. When that doesn't work, he shouts at her that they're meant to be together, frightening the poor girl. (Oblivious to the fact that his overbearing attention towards her was what made her break up with him during Jessie's bat miztvah). When he sees Nick's nipples have swollen, instead of showing his usual empathy he and Jay start agitating them in a public place, which causes Nick to start crying uncontrollably. Andrew then spoils Lola's party by destroying a television, pushing Missy even further away and trying to convince everyone that Lars was faking his disability (which Maurice repeatedly tried to talk him out of).
- Jay's attempts at polyamory take a physical toll on him and he tearfully breaks up with his fuck-buddies. The fact that they left through a disappearing act just sells the finality of it.
- One of the extras is a pair of incestuous conjoined twins who break up at the restaurant. When Eliot begins the incision to separate the two, his hand twitches and one of the brothers flatlines.
- Amid an already bleak episode, Coach Steve casually mentions having suicidal thoughts ever since he lost his job. His only real coping mechanism is a makeshift girlfriend that spouts pre-recorded lovey-dovey lines.
- Connie's emotional, full-throated rendition of Changes will absolutely shake you.
- Charles Bradley, whose cover of "Changes" is the theme song, died one week before the series premiere.