The book begins with Tally, the protagonist, as a Pretty debating what to wear to a bash. While attending the bash at which she is to be voted into the "Crims" clique, she is followed by someone who appears to be a "Special", a member of Special Circumstances, which brings back many memories.
Tally can only remember her adventures as an Ugly in brief, disconnected bits because of the brain lesions present on all those who have undergone 'the Operation'. She is surprised to discover that the person stalking her is Croy, an old friend of hers from the Smoke. He has something for her, he tells her, but she must search for it later. She agrees, bemused by his repellent ugliness, including his big pores and tangled hair – all the imperfections that the surgery to become a Pretty transforms into beauty. Later, she wonders why she felt so strange until she takes the pill. Tally returns to her care-free life as a pretty. Her peace is disrupted when Zane, who is the leader of the Crims, asks her about David, whom she loved while she lived in the Smoke (the rebel community).
Zane had once known Croy and had been determined to escape to the Smoke before his surgery. He regrets that he didn't go into the wilderness then. Zane is eager to accompany Tally in finding the object Croy has hidden for her. They face strenuous, dangerous physical challenges in order to locate the item, which is accompanied by a letter from Tally to herself, written before she went under the knife. The letter explained to her future self why she had become a Pretty – to take a brain lesion cure pill.
Zane and Tally learn that the Pretties' brains are altered during their surgery. After taking the pills, their main goal is to be bubbly. "Bubbly" is Pretty slang for "cool," also referring to a state of having a natural high or being full of adrenaline. The adrenaline rush helps cut through the "pretty haze," and enables clearer thinking. They try to help all the Crims stay bubbly. They do things to make the Crims bubbly, such as crashing a skating rink.
When Shay, who, after becoming bubbly, remembered how Tally betrayed her, questions why Tally is bubblier than the rest of the clique, Tally told Shay about the pills. This makes Shay furious because she wanted Tally to share the pills with her. Shay forms a new clique known as the Cutters, who cut themselves to stay bubbly. Knowing that Special Circumstances will come after her any minute, Tally decides that she must go to the New Smoke. Meanwhile Zane is suffering extreme headaches and finding it hard to do everyday tasks. Thinking that this has something to do with the pills, they go to the New Smoke in a hot air balloon, taking the risk of dropping more than 500 feet in the air.
Peris decides in the balloon that he does not want to go to the New Smoke. He stalls Tally, and instead of falling to the river, she falls into a reservation with rather primitive people who seem to be very violent. She is considered a god there because of her beauty. There she meets Andrew Simpson Smith, who is the only one who speaks her language. When she escapes the reservation, she goes to the Rusty ruins. When she calls, she sees someone coming down on a hover board and is shocked to find that it is David who has come to take her to the New Smoke. When she arrives, Maddy tells her that the pills she and Zane took separately were meant to be taken together by one person. The nanos that were supposed to eat away the lesions, but they ate more of Zane’s brain tissue because they needed the pill that Tally took to stop them. This means that the pill Tally took did nothing, she thought her way out of being Pretty, a feat that was thought impossible. They soon discover that, when Zane went to the hospital for his headaches, a tracker chip was put in his tooth that sent a message to the Specials. Tally decides to stay with Zane instead of escaping with David. David is confused and believes that she only loves Zane because he is a Pretty, and tells her so. To make David leave and not get caught himself, Tally tells him to "get his ugly face out of here", hurting him. It had the desired result and he flees. She stays with Zane which leads to her getting caught by the Specials. When she is at the Specials office she discovers Shay has been turned into a Special. The book ends with Shay forcing Tally to turn into a Special, too, as Shay's revenge.
The protagonist of the story. Early in the book she falls in love with Zane (forgetting about David) and she and Zane find "the Cure". She finds out from Maddy that she really wasn't cured, that she thought her way out of the Pretty mind state.
The new love of Tally. He was the leader of the Crims. Zane knew some of the people in the Smoke and had been determined to escape to the Smoke before his surgery. He decided not to at the last minute. He was captured by the Specials and was threatened: he had to tell about the Smoke, or they would turn him into a Special. He tells the Specials what he knew and then they turned their attention to Shay. He has brain damage from taking one of the pills.
A best friend of Tally until she finds out that Tally shared "The Cure" with Zane instead of her. She then feels betrayed by Tally and tries to find her own cure. She then becomes a "Cutter", an improved special, and revenges on her.
David is still in love with Tally from when she was an ugly. He is the one that rescues her from the wild and takes her to the New Smoke. Tally no longer loves him the same way David loves her.
The best friend of Tally (along with Shay). He is part of the "Crims", a group of troublemakers. He chickens out at the end and does not go to the Smoke with Zane and Tally.
Friend of Peris who is also part of the "Crims." He escaped to the New Smoke.
David's mother. She invented the cure. She tells Tally that the second pill was meant to stop the nanos in the first pill from eating away the brain. Without it, the nanos would eat the brain, as seen in Zane. She doesn't like Tally very much after she accidentally led the Special Circumstances to the Smoke and after the death of Az, David's father, but does not blame Tally out loud.
Head of Special Circumstance, the reason why Tally was sent to Smoke. Creator of Project "Cutters"
He appeared at the party dressed in a Special Circumstances costume and followed Tally. He told her where to find the pills and he was her friend at the smoke.