Rylant wrote Missing May in the first person, revealing the thoughts and feelings of the grieving protagonist, Summer, who goes to live with her Aunt May and Uncle Ob when she is six years old. Summer's mother has died and none of her mother's brothers and sisters in Ohio want to be bothered with her. When she arrives at the run-down trailer in Deep River, West Virginia, that Ob and May call home, Summer discovers a family of her own — and enough love to last her a life time.
For six years, Summer feels like "she's died and gone to heaven." Her life is perfect. May takes care of Summer and Ob and enjoys her "gardening." Ob creates whirligigs that represent abstract ideas or things such as May's spirit, hope, heaven, love, dreams, and death, which they call The Mysteries. Summer goes to school and lives what she considers to be a normal life. But when Summer is 12 years old, her world is turned upside down. May dies suddenly while working in her garden. Ob and Summer are devastated. They don't know how to go on without May. Within a short time, Ob reveals to Summer that May's spirit has visited him. Summer becomes concerned about Ob. She is afraid that Ob will want to be with May and that he will die and she will be left alone.
Cletus Underwood, a classmate of Summer's (who she would rather not be associated with), befriends Ob (and later, Summer). Cletus begins to spend a lot of time at their trailer listening to Ob tell about May's "visits." Cletus is nonjudgmental and is empathetic toward Ob. Because Cletus had a near-death experience as a small child, Ob becomes convinced that Cletus can help him communicate with May's spirit. Ob wants to install him like some "afterlife antenna." Cletus shows Ob an advertisement about a medium, named Reverend Young, who communicates with the dead. He suggests that they go to Putnam County to find Reverend Young and stop at the state capitol in Charleston on the way home. Ob, Cletus, and Summer look forward to the trip. Summer hopes that contacting May through Reverend Young will alleviate Ob's depression and give him a reason to keep going. They are crushed when they arrive in Putnam County only to discover that Reverend Young has died. Ob decides to return home. Summer and Cletus do not mention their plan to stop at the state capitol.
As they pass the capitol, "Right out of the blue, [Ob] wanted to live again." Not wanting to disappoint Summer and Cletus, he turns the car around and goes back to the capitol where they spend an enjoyable day. They return home that night and as they are taking their belongings out of the car (Cletus is going to spend the night), an owl flies overhead. The owl reminds summer of May and how much she misses her. Summer cries for the first time since May's death. The next morning, Ob, Summer, and Cletus take all of Ob's whirligigs out to May's garden where they erect them. They set the whirligigs free, along with May's spirit, and find consolation in their memories of May.