Despite being banned for life from the comic book store, Bart and Milhouse take over its management when Comic Book Guy suffers from a cardiac episode, which he calls "worst episode ever". Their management of the shop is fairly successful, until they discover Comic Book Guy's secret stash of illegal video clips and begin charging admission for their viewing. Meanwhile, Comic Book Guy on the road to recovery receives tips from Homer on making friends, to no avail, until a chance meeting with Principal Skinner's mother sparks an unusual relationship.
The episode begins with Marge making pancakes for the family breakfast. When Lisa goes to get the syrup, she notices a very old box of odor absorbing baking soda at the back of the fridge. Homer makes a bet with Bart that he can eat the whole box for $50, and after one bite, Homer has an "antacid trip" and is unable to finish. Bart takes his newly won $50 and goes on a spending spree with Milhouse.
After spending $40, Bart and Milhouse go to The Android's Dungeon & Baseball Card Shop and attempt to buy a new edition of Radioactive Man. While there, Martha Prince (Martin's mother) shows up with a box of items to sell to Comic Book Guy, but unbeknownst to her, the old box of "junk" is actually her son's original and very rare Star Wars memorabilia. Comic Book Guy offers her a very low price, but Bart and Milhouse convince her not to sell it. Consequently, they are banned for life from the store.
Lisa and Marge see a notice in the paper that a show by Tom Savini will be performed in the Android's Dungeon. Bart and Milhouse try to sneak in by carrying Homer on their shoulders, wearing a trench coat under the guise of Shaquile O'Neal. However, Comic Book Guy had previously been tipped off to the plan by Homer for a bribe, and they are prevented from entering the show.
During the show, Tom Savini plays several pranks on Comic Book Guy, humiliating him. Just before he finishes an angry rant where he proclaims that everyone is banned from his store, Comic Book Guy has a massive heart attack. At the hospital after the ordeal, Dr. Hibbert orders Comic Book Guy to relieve his stress by taking a break from running the store. Bart and Milhouse had called 911 and saved Comic Book Guy, so to make it up to them, he allows them to manage the store during his absence. Their management of the store goes well (with Bart ordering Milhouse around) until, in an attempt to impress Lisa, Milhouse makes a bold management decision to buy 2000 copies of a comic called "Biclops", a comic sold by Plan 9 Comics and published by Lens Crafters about a glasses-wearing super hero (who resembles Milhouse).
Meanwhile, Comic Book Guy has been searching for human companionship. After being called a manatee at Moe's Tavern, he returns by first insulting Duff and then air conditioners, upsetting everyone and getting himself ejected from the bar. On his way to a group therapy session, he bumps into Agnes Skinner. They exchange insults, falling in love and beginning a torrid relationship.
Milhouse's purchase decision, of course, proves to be poor as the comic is very unpopular to potential customers, but he had spent all the money on "Biclops". Bart and Milhouse start fighting over their predicament and accidentally stumble upon Comic Book Guy's secret (and illegal) video stash. In order to recoup their losses, Milhouse hatches a plan to sell tickets to a midnight showing of the videos in there (which include CCTV footage of various actions by the townspeople and a stolen video tape of Ned Flanders revealing that Homer released a radioactive ape into his house).
Comic Book Guy picks up Agnes Skinner for a date, and their love affair continues spurred by insulting and humiliating random people.
During the midnight bootleg showing back at The Android's Dungeon & Baseball Card Shop, the group is busted by Chief Wiggum and the police. Milhouse tells the police that the video stash is not theirs and the police go on to bust Comic Book Guy. They break in on him and Agnes Skinner making out in their bathrobes on the bed. Eddie vomits and Chief Wiggum offers to reduce the sentence if Comic Book Guy puts some pants on. The police cuff him and take him away as he bids farewell to Agnes.
The episode ends with Bart and Milhouse walking away from the store, now an evidence scene, and claiming everything is "back to normal". However, the ape seems to still be living with Ned.
The episode was written by Larry Doyle (his last Simpsons credit) and directed Matthew Nastuk. The picture of Matt Groening on the list of people banned from The Android's Dungeon & Baseball Card Shop is sometimes credited as George Lucas. There was an in-joke on the title of newspaper Lisa reads with the staff trying to figure out how to set up the dinner-scene and decided to add a newspaper called "The Daily Set-Up". The joke where Ralph says everyone is hugging was originally supposed to be "she's hungry", but was changed as it was though to be to inappropriate. The scene where Ralph goes in the adult section is Hank Azaria's favorite joke from the episode.
The episode was named a "classic" by several critics, who reviewed it. Matt Groening called it "a very special story" and was ranked #12 in the Top 20 Best Episodes List which was listed by AOL. Hank Azaria won Primetime Emmy Award for Outstanding Voice-Over Performance for voicing Comic Book Guy.