Tara Sullivan, the narrator of Kissing Doorknobs, is a young girl who feels like she is taken over by 'tyrants' who make her think thoughts she can't control. It starts with the singsong 'Step on a crack, break your mother's back', which repeats endlessly, no matter what she is doing. As she pays too-close attention to the things around her, she begins to worry as well, and then her anxieties won't shut off. Things get worse and worse for Tara as her 'quirks' alienate her friends and exasperate her family, but she never feels like she can stop. She finally gets relief when a friend of father's tells her that she might have obsessive compulsive disorder, which is a condition shared by millions of other people. With a diagnosis, she starts to see a therapist, and get control over the 'tyrants' and the things they're always telling her.

Tara's story begins when she is in fifth grade and she starts to repeat "Step on a crack, break your mother's back," and then to obsessively count cracks in the sidewalk. She pushes her friends, Keesha, Anna and Kristin away, sometimes literally, when they interrupt her, but she cannot explain why she needs to count or why she is so impatient to be interrupted. There are light moments where it seems like Tara might be able to compensate for her strange habits, and when she tells her friends about them, they love her anyway, but the problems get worse and worse over time, and eventually she drives her friends away.

The biggest problem for Tara is her relationship with her mother, for her mother's nerves are completely shot with Tara's obsessive counting, and then with her habit of praying all the time. Tara can't stop this behavior, but her mother ends up trying to shake it out of her, or slap it out of her, and the low point of their relationship comes at the carnival when Tara's mother shakes her violently because Tara has been crossing herself all through a ride.

Things seem like they might be getting better for Tara in eighth grade, when she befriends a tough girl named Donna DeLuca, whose parents are never home. Donna doesn't judge Tara, so Tara doesn't have as many reasons for strange behavior with her, but her freedom only gives her more room to be anxious about things, and it doesn't sit well with her family, who are still upset about her compulsive behavior. Another low point comes at Christmas, when Tara needs everyone to sit in their accustomed seats—her father stalks out, and her mother and grandparents leave as well, and the meal is ruined.

Things turn around for Tara when her father's friend Mr. Jacobson comes over and recognizes some of Tara's behaviors. He tells her that she might have obsessive compulsive disorder, and he puts her in touch with a boy named Sam who used to wash his hands compulsively out of a fear of contamination. Tara gets help from Susan Leopardi, a therapist, and begins to overcome her fears and repetitive behaviors by imagining the things that make her most afraid, and trying to diminish their effect. In the end, Tara gets to prove her recovery by being the one who gives Sam encouragement and advice when the death of his pet parakeet sends him back into obsessive behavior and fears.