The novel The Counterlife tells multiple versions of the same story. Sometimes the stories seem to be slight modifications of others, and other times the stories are complete and drastic revisions.

Part 1 tells the story of Henry Zuckerman, who risks his life undergoing heart surgery so he can stop taking medication that has deprived him of his sexual potency. Not yet forty, the dentist Henry cannot face life without the ability to have sex with either his wife or his mistress and assistant. Though the doctor tries to convince him not to have the risky operation, Henry is determined. Shortly before his operation, Henry confides in his older brother, Nathan, his predicament and his desire to restore his virility, and it is Nathan who tries to understand what drives his brother to such drastic measures.

In Part 2, Henry does not die from the surgery, but his emotional recovery from the operation is lacking. Though the operation is a success physically, Henry senses emptiness in his life. During a leisure trip to Israel, Henry feels like he has lost touch with his Jewish heritage. This notion persists even after Henry returns to the United States, and one day without warning Henry leaves his dental office and boards a plane to Israel. Nathan goes to Israel to meet with Henry in an effort to get some answers about Henry's unexpected actions.

During his time in Israel, Nathan meets many unforgettable characters. Nathan, who has never thought much of his Jewish heritage beyond its potential for humor in his many novels, has difficulty understanding the religious and patriotic passions of the residents of the Israeli settlements.

Part 3 consists of an in-flight adventure of Nathan's. What begins as an absurdly comic notion of a young man to hijack the plane for the benefit of the Jewish people ends in a situation devoid of any humor.

In Part 4, Nathan, not Henry, has died from complications during heart surgery. Unlike Henry's reasons for risking surgery to regain the ability to have recreational sex, Nathan risks the surgery so he can become a father. Henry tries to attend the funeral in order to put some grievances toward his older brother to rest, but first his brother's eulogy that praises the very book that caused the estrangement and then the discovery of an unpublished manuscripts reignites all of Henry's anger toward Nathan.

Part 5 seems to take place in England where Nathan has recently moved after marrying an Englishwoman, Maria. Maria is five months pregnant with their child, and they look forward to a happy life together. They are remodeling a home in the Greater London area, and both Maria and Nathan believe that they have reached the happiest moments yet in their lives. Nathan's exposure to both the English class system and his first experience with overt anti-Semitism cause him to reevaluate his plans, and the ensuing discussion leads to a serious and damaging argument with his new wife. The argument also provides some clues as to how the different versions of the same stories relate to each other.