- In general: Mac's mom is always at work, we never see his dad, he's constantly tortured daily by his older brother, it's implied that he doesn't have any friends at school and is a common target for bullies, his imaginary friend is a huge jerk to him yet he's so sweet that he still visits him every day.
- Even worse, as pointed out under Fridge Horror, Bloo is supposed to be based on a security blanket but because of Mac's upbringing, he can't fathom a security that doesn't involve being abused. So the closest thing he has to a best friend is an abusive jerk.
- Bloo and Mac having to split up in the pilot episode, especially after Mr. Herriman shamelessly breaks their spirits by telling Bloo to his fact that Mac is never coming back. He's seen it a million times.
Terrance: Where were you, anyway, stupid? What are those stupid eggs, stupid?? Where's that stupid little blue friend of yours, stupid? Mom told ya to get rid of him!! Ho-ho-hoo boy! If you didn't, you're gonna be so-Mac: (finally turning around and screaming): I WAS NOWHERE AND THEY'RE NOTHING AND I TOOK CARE OF IT!! HAPPY?!(Terrance looks at him, speechless, as Mac slams his bedroom door behind him).
- Mac coming home from his first visit to Foster's after dropping off Bloo, with a handful of Coco's eggs. He just walks glumly back to his room while Terrance follows and repeatedly smacks him in the back of his head.
- When you think about it, it's rather sad that all of these regular characters are imaginary friends ready to be adopted, but who no child wants, apparently.
- The series finale. Looks like Mac's moving away! Well he did move. Just to the apartment next to his because his mom needed a larger working space.
- Good Wilt hunting reveals Wilt's past. Wilt ran away from his kid when they lost a basketball game, and thought that he could never forgive him. Turns out, this hurt him more than anything, and the flashback scene at their reunion is heart-wrenching.
- You can't help but feel sorry for Frankie missing the concert in "Imposter's Home for... Um Make 'em up Pals".
- The episode that first introduced Goo. She spends most of the episode being loud, talkative, clumsy, and obnoxious, incessantly accidentally creating countless imaginary friends which became residents of the house, leading to the house getting overcrowded. Mac tries to get her to stop, but she is oblivious to the fact that she is causing problems. And as everyone believes it's Mac who keeps letting her into Fosters and has a crush on her (in both cases, it's really Bloo) when the house eventually becomes so crowded they main cast has to sleep on bus, Frankie and Mr. Herriman sympathetically but firmly tell Mac that he is no longer allowed at Fosters because he "can't stop bringing Goo there". Even worse, the deal to keep Bloo from getting adopted by another kid will be broken if Mac doesn't stop Goo from coming. Then everyone gives Mac a sad look (except Bloo who gives an apologetic look, since he was really responsible.) The message is clear: either Goo goes or both Goo and Mac go. Mac then releases a shocking "The Reason You Suck" Speech... which leads to Goo's eyes welling up with tears, and the girl just leaves to hide in one of the rooms. That's when Mac finds out Goo made him a gift: she fixed his backpack after accidentally tearing the straps earlier in the episode. Mac later finds Goo in a room crying, and she tearfully admits that the reason she creates so many imaginary friends is because she has no real friends. She then verbally abuses herself for being such an annoying screw-up. This leads to a Heartwarming Moment when Mac takes back everything he said, apologizes, and comforts the poor girl, telling her that he likes her and appreciates her imagination and niceness. Goo then responds by giving Mac a big hug.
- The speech from Mac itself is acidic enough:Mac: I don't like you! (Beat) Don't you get it? Nobody likes you! You're annoying and weird and you talk too much and Bloo's name is not Chester, Mr. Herriman is not a badger, that's not how you play checkers, and protein doesn't come from bananas, it comes from nuts, which you don't need to eat more of because you are nuts! You're chock full of nuts! You're so nuts, you drive ME nuts! (Jumps in Goo's face) Get it? Get it? Get it? Get it? Get it? Get it? Get it?! Everybody thinks you're a nuisance and they all want you to just GO HOME!!!
- The speech from Mac itself is acidic enough:
- The Book-Ends finale shot. After years of seeing the house be drawn as part of the opening title sequence, the cast of the show finally say goodbye by un-drawing the house in the final shot.
- Cheese: Okay, bye, doggies!
- "Why everyone hurt Red?"
- "Red kill flowers..."
- In "The Sweet Stench of Success"
Bloo: (weakly) Have...B.O.? Get...Deo.
- Bloo enjoys living the life of luxury But then his producer Kip refuses to let him leave and makes him to sleep in a cage. He is then forced to attend several gigs and conventions which he quickly becomes bored of.
Mac: I can't believe he didn't say hi to us.
- Mac and the gang try to visit Bloo at his Deo gig, but the guard won't let him in with no ticket. Mac calls out for Bloo, but Bloo can hardly see Mac among the massive crowd before Kip drags him away.
- Later the others sit on the Foster porch and Mac believes that Bloo doesn't care about him anymore due to his newfound fame.
Frankie: Well, maybe he didn't see you.
Mac: Oh, he saw us! I guess he's just too big of a star now.
Eduardo: No! Must be another reason!
Coco: Coco! Coco!
Mac: He looked me right in the eyes and I looked into his!
Wilt: What'd you see?
Bloo: Lemme call Mac just once! I miss him!
- Bloo desperately begging Kip to let him contact his friends, only to be cruelly rejected once more.
Kip: I told ya, you don't need him anymore it's easier if you cut him off cold turkey.
Kip: Hey! Celebrities don't complain! (turns off the lights with a devious smirk, then closes the door as Bloo's eyes well up with tears)
- Followed scene where Mac and Bloo are sad about being away from each other, and a montage plays over their sadness.
Kip: Deo, honey, baby! Why ain't you dressed? We gotta go-go-go!
- When Bloo tells Kip that he quits and just wants to go home, Kip drops his nice guy act and reveals his true colors: a jerk who doesn't care about Bloo's well being and he tells Bloo that the contract he signed wasn't an acting contract but adoption forms, thus Bloo has no choice in the matter. Bloo pleads this isn't what he wanted but Kip still heartlessly blows him off.
Bloo: NO! I'm not doing any more appearances, corporate speaking gigs, sleeping in a cage or sticking my head into some guys underarm ever again! I quit!
Kip: What're you saying, kid? Don't mince words.
Bloo: I quit! I just wanna get something to eat, then go home to see my friends! I quit!
Kip: You can't quit.
Bloo: Sure, I can. Watch. I! QUIT!
Kip: I own you, kid. That contract you signed—that wasn't an acting contract. It was adoption papers. So, as your legal gaurdian, I say YOU CAN'T QUIT!
Bloo: But... I didn't wanna be adopted!
Kip: "But I didn't wanna be adopted!" Well, you shouldn't have gone on TV saying that you did! You asked for this! Now, you are gonna get into your little costume and you're gonna perform your live variety show to millions of viewers like we planned! YA GOT THAT, PUNK?!
Bloo: (gulps) Y-Y-Yes, sir...
Wilt: Mac! The Deo Variety Hour is about to start!
- Mac stands with his back to the TV and rants about how Bloo has been "ignoring" him.
Mac: I don't care! I'm not watching!
Mac: 'Cause Bloo doesn't care about us anymore! So why should I care about him? He hasn't been home in forever! He hasn't called in weeks! He didn't even acknowledge us when we saw him!
Eduardo: But es Bloo! Your amigo!
Max: Not anymore, Ed. Not anymore.
- In "Who Let The Dogs In", when Eduardo says goodbye to the puppies and one of them snuggles into his arm before Frankie takes him away. The look on his face afterwards is heartbreaking.
- In "Affair Weather Friends", a sugar-crazed Mac's acting out of an imagined conversation between him and Bloo where he imagines Bloo insulting him, saying he doesn't need Mac, and leaving for good. It shows that his biggest fear is losing his best friend.
- Mr. Herriman's verbal beatdown of World in "Destination Imagination". It's the scolding every kid dreads, and World looks like he's having a freakin' panic attack!
- What follows is World having a full on mental breakdown, letting out Big "NO!" after Big "NO!" screaming "NO NO NO NO NO NO NO! I WON'T LET YOU LEAVE WITH HER! GIVE HER BACK! YOU CAN'T TAKE HER FROM ME! SHE'S MINE! MINE MINE MINE MINE MINE MINE MIIIINE!" as we're treated to a visual representation of his state of mind while the gang flees for their lives - his world literally coming apart.
- Frankie's backstory according to the Tweets made by Craig McCracken. Because Frankie's dad (who was also Madame Foster's son) was disillusioned over Imaginary Friends thanks to his experiences with Mr. Herriman, Frankie was never allowed to have or create one, and she was forced to get rid of the only one she actually got to create thanks to her dad. Her main reason for living with her grandma in Foster's Home instead of with her parents? So she could see that same Imaginary Friend she herself created again someday.
- Even if she is an Ethnic Scrappy with an annoying singing voice, Eurotrish gets quite a raw deal in "Foster's Goes to Europe". Not only does Bloo keep on rudely denying Eurotrish her chances to go back to Europe, but the scene that plays during the credits shows Eurotrish finally making it to her creator's home, only for her creator to turn her away because she couldn't stand her singing. It's especially heartbreaking when you take into account that most creators in this series are shown to be loving and caring toward their imaginary friends even in adulthood.
Tearjerker / Foster's Home for Imaginary Friends