Jerri tries to do things the right way but always ends up learning the wrong lesson. Her hijinks often involve, either directly or indirectly, history teacher Chuck Noblet and his secret lover art teacher Geoffrey Jellineck. Every episode features a warped theme or moral lesson and ends with the cast and other featured actors from the episode dancing. The last episode features Flatpoint High being turned into a strip mall, a development that reflected Comedy Central cancelling the show to make room for a TV show called Strip Mall.
At first, Sedaris wanted to do a straight after-school special: "We wanted to play it dead, dead serious. No laugh track, nothing. But Comedy Central didn’t go for it." Rouse, Colbert, and Dinello went to the Museum Of Television and found several after-school specials starring Scott Baio, which they used as reference. Dinello later found a tape of Florrie Fisher's The Trip Back at Kim's video in the East Village; Fisher, a motivational speaker, recalled her days as a New York prostitute and heroin addict to a group of high-school students. After watching it, Dinello thought Fisher reminded him of Sedaris and promptly suggested doing a character—inspired by Fisher—that would go back to high school. Colbert added the idea of her learning the wrong lesson after every episode, and Sedaris said "Okay, she'll be a junkie whore this time." Rouse noted Strangers was a combination of Fisher's tape, the Baio specials, Aileen Wuornos: The Selling of a Serial Killer, and Frederick Wiseman’s Titicut Follies.
Colbert, Dinello and Sedaris wrote most of the episodes. The process started with an "overlying outline": knowing the start and the end of the episode, they would build the scenes in between and later would improvise together in a room. Whatever they laughed at went in the script. Colbert later said of this method: "Our rule was, if it makes us laugh, we put it in the script. There was not a single thing said by a character in that show that was right. Every choice was the wrong moral choice. Because of the freedom Comedy Central allowed us, we said and did things that were outrageous and extreme." They would also keep typos in. Sedaris recalled: "That's what I learned from working on Strangers. If you're not laughing, how do you expect anyone else to laugh?" Alterman said of the show's structure "The way we approached [it] was to present each one as a morality play where in the third act the protagonist, Jerri Blank, would always, without fail, make the wrong choice. And then to cap it off, she would come back in the epilogue in the fourth act to say what she learned, and she would also draw the wrong lesson from the wrong choice she had made." To absolve themselves of the offensive stuff they had written, they would imagine all the scripts were written by a middle-aged woman named Jocelyn Hershey Guest, in a similar way to J.D. Salinger alter ego Buddy Glass. "In the world where she’s writing, these are the right moral choices," Colbert has said. Very occasionally they would write with a collaborator such as Cindy Caponera, Mitch Rouse, or Thomas Lennon. Some of Jerri's phrases like "You got skills to pay the bills" and "I like the pole and the hole" came from things Sedaris' brother Paul would say. Much of Jerri's past is taken from anecdotes in The Trip Back, some of which are also in Fisher's autobiography, The Lonely Trip Back. Several lines of dialogue in the series were taken verbatim from Fisher's public-service film. Sedaris would often watch the show without sound to see if a deaf person could follow: "Okay, if I couldn't hear or understand anything, could I still find the show entertaining?" And I did. 'Cause everyone was so interesting to look at." The third season was written in Charleston, South Carolina, Colbert's hometown.
Comedy Central picked up the series in 1998 after Colbert had already begun working on The Daily Show. As a result, he accepted a reduced role, filming only around 20 Daily Show segments a year while he worked on the new series. The show was originally entitled The Way After School Special, but later was changed to Strangers With Candy, which was just a name they had come up with years earlier, and had been wanting to use for one of their projects. It came from the phrase "Don't take candy from strangers," which would probably be a lesson from an after school special. Sedaris has credited producer Kent Alterman with the development of the show: "He really helped us shape that show. We went in there with strong ideas, but he changed it a lot from the pilot to the first episode. He had a good eye and really good ideas, and we trusted him from the get-go." Doug Herzog, who was at the time, president of Comedy Central's parent company Viacom, also noted his influence, "Kent recognized the brilliance and genius of Strangers With Candy really early on. He really championed it when a lot of us were looking at it, going, “What is this?” The show faced slight censorship from the network, Sedaris said, "It was weird. Like they let you say "pussy," but not "faggot" — until the fourth show. They said, "You have to build up to 'faggot.'" And the script of one show had me writing in my "dirty, filthy Jew diary." Well, I could say "dirty," but I couldn't say "filthy." It was killing me." Mostly, however, the writers were left alone to their own devices.
Vicki Farrell designed the wardrobe for the show. When designing Jerri Blank's appearance, Sedaris told Farrell "I want to look like I own a snake." Jerri would often wear high-waisted pants and snakeskin ankle boots, as well as turtlenecks because Comedy Central did not want track marks or tattoos to be visible. To complete the look Sedaris wore a fatsuit. Some of her clothes were custom made or came from thrift stores. Sedaris wore a wig and fake lashes, and told the hair and makeup department she wanted Jerri to look like a professional golfer. It would take about 40 minutes for Sedaris to get into character.
When writing the pilot, the writers would perform the characters, and realized that they were imitating Greg Hollimon when they read Principal Blackman's lines. Colbert called Hollimon to play the part, but his mother, who had dementia, forgot to pass him the message. A few weeks later Rose Abdoo was able to contact him, and he flew to New York to film. The creators, Hollimon, and many other stars of the series, were also alumni of Chicago's Second City. Roberto Gari was chosen for the role of Jerri's father Guy as he was the only actor who was able to do the character's poses and keep still for a long period of time.
In 2003, Dinello said of the show's cult status: "People were angered by it or fanatical about it. We were mocking the conventions of after-school specials and most of what you see on television--how easily things are sewn up, how false relationships are." In a panel with Levy, when asked about why they think the show had such a dedicated fanbase, Dinello and Sedaris said, "We embrace losers, misfits and outcasts." Sedaris has described the audience for the show as "Drag Queens getting ready on a Friday at 5:30." as well as "Homosexuals and 14-year-olds and farmers and ghosts." She has also said, "I’m just glad it still lives on. It’s fun to know that you threw a hole on the wall, you went through it, you did this show that you didn’t know what it was, and now there’s a whole new generation of kids watching it. It’s still out there and still alive, and we’re all really proud of it. Colbert echoed the statement: "It's a badge of honor that I served Amy's comedic vision. I could do hack shit for the rest of my life, but I'd go, "Yeah, but I also wrote that stuff." In 2024 he described the show's fan base as "deeply troubled," continuing, "And I’m happy for them, because I’m deeply troubled too."
The initial theatrical release was June 28, 2006, in the New York City area, followed by the remainder of the United States on July 7. A DVD of the film was released in November 2006. Amy Sedaris said of Jerri Blank that "she's like a rash; you never know when she's going to pop up."
In 2024, it was revealed that the creators had been approached about a revival of the series, which they have declined as "Nothing has felt right so far". Regardless, they have not brushed off the possibility of it coming back in some way. Dinello noted: "Everybody seems game to do something. But we need an adult to make it happen". Although Sedaris has brought up concerns about the difficulty to make the show now, due to its un-PC humor, Colbert has disagreed, "You can make anything you want, you just have to deal with people being upset".
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