* Meta example: [[http://en.m.wikipedia.org/wiki/Christine_Cavanaugh The retirement, and eventual death]], of Creator/ChristineCavanaugh, the original voice of Dexter.
** Another meta example: This song by The Nobles, [[https://www.youtube.com/watch?v=8j-MhR4Nq30 "Mandark"]]. It's about how Mandark is Dexter's enemy because [[AlwaysSomeoneBetter he pales in comparison to Dex]] and just wants to prove that he's also a genius. What's truly sad is that it's [[GeniusBonus pretty]] [[FridgeBrilliance accurate]] to how Mandark was introduced and characterized (at least earlier on in the show), especially if you've seen "Mandarker" (mentioned below).
* The wacky and fun episode of Dexter having to deal with Dee Dee's imaginary friend hanging out with him ends with [[spoiler: Dexter wishing away the imaginary friend, and commanding him to never come back again. And he does. Dee Dee runs away sobbing.]] Then it fades to credits where Koosie just laughs and it suddenly becomes NightmareFuel.
** Dexter [[HeelRealization feels so guilty]] that he finally gives Koosie the hug he's been wanting the whole episode.
--> '''Dexter''': You ARE warm...
--> '''Koosie''': Hee hee hee, I know.
** And on top of that, it's also part HarsherInHindsight, and part DownerEnding due to Creator/DomDeLuise passing away.
* The ending to "Way of the Dee Dee" with Dexter solemnly repairing his destroyed lab (that he wrecked ''himself''), as Dee Dee runs off in tears.
** Dee Dee's ''[[MyGodWhatHaveIDone horrified]]'' reaction as Dexter wrecks his own lab is even worse-- [[GoneHorriblyWrong and it all started with her trying to get Dexter to lighten up a bit.]]
* Dad's speech about Pet Heaven in "Filet of Soul".
* Mandark's dream at the beginning of "Mandarker".
* Dexter's operatic solo at the end of "[=LABretto=]".
** And before that, Dee Dee wrecking his every invention and driving him to despair, him finding solace in starting his laboratory, and the first time she ever enters his lab...
--> '''Dee Dee''': Ooohhh, WhatDoesThisButtonDo
--> '''Dexter''' (Voice breaking, after witnessing [[WalkingDisasterArea all of the destruction she has done]], and knowing what the [[BigRedButton button]] ''[[SelfDestructSequence will]]'' do): ''What have I'' '''ever''' ''done to you?''
* The episode "Dee Dee's Tail" is about Dee Dee convincing Dexter to turn her into a horse and, as you can imagine, she is very happy... Until she realizes her brother and her friends just want to use her for rides, not caring if she is tired (even when she is lying down after taking her friends for a ride the whole day, all they do is show her a chariot they want her to pull). Realizing that the people you love just want to use you and don't care for your feelings is really sad.
--> '''Dee Dee''': This is terrible... First my brother and now my best friends... (Crying) I wish someone would help me...
* As quoted from Fridge Horror: "When watching ''WesternAnimation/DextersLaboratory'', if you think about it too much, you'll realize what a cruel, destructive jerk [=Dee Dee=] really is. When she's not completely destroying her brother's life's work, she at times openly belittles, insults, humiliates, and abuses him for kicks and giggles." You need only look at such episodes as Road Rash, The Big Cheese, [=LABretto=], Framed, Sister Mom, Dimwit Dexter... you get the picture.
** This is doubly worse when you think back to the few times that Dee Dee herself is in trouble. You can tell that despite everything, Dexter has some serious BigBrotherInstinct going on, despite being the younger brother who gets put through hell by his sister. That says nothing good about Dee Dee and a lot of good about Dexter.
* Dexter's slinking away from his family in ''Old Man Dexter'' after being shot down when wanting to spend time with them because he's not old enough is treated to a few oddly long shots without any comic gags in them. Anyone who was the youngest child (or TheUnfavorite) in their family can identify with him.
* The GratuitousFrench episode. He's solved all the world's problems with the term ''omelette du fromage''. One problem: It's not the password of his Laboratory. He panics as the Laboratory erases its memory banks and shuts down.
** ...if by "shuts down" [[FromBadToWorse you mean]] "[[spoiler:'''blows the fuck up''']]" as Dee Dee ''taunts him''...
--->'''Dee Dee''': ''That's all you can say! That's all you can say!''
* Seeing young adult Dexter in 'Ego Trip'. It's really depressing to see Dexter, a boisterous, precocious little boy become neurotic and cowardly. The scene with Mandark whipping him is especially hard to watch.
* In his first appearance, Mandark forcing Dexter to shut down his lab.
-->'''Computer''': "What are you doing, Dexter?"
-->'''Dexter''': "Goodbye, my love."