Their families dead from the pandemic SitkaAZ13, known as "Pest," 15-year-old cheerleader Clare and 13-year-old chess club member Jem are thrown together. They realize that, if either of them wishes to reach adulthood, they must find a cure. A shadowy adult broadcasting on the radio to all orphaned children promises just that—to cure children once they grow into Pest and then to feed and care for them.

Or does this adult have something else in mind? Against a hostile landscape of rotting cities and a countryside infected by corpses and roamed by diseased and doomed survivors, Jem and Clare make their bid for life. As their group of fellow child-travelers grows, they embark on a journey to find the cure. In their search, they are hampered by the knowledge that everything in this new world has become suspect—adults, alliances, trust, hope. But perhaps friendship has its own kind of healing power. And perhaps, out of friendship, there can come love.