Louis Ortiz is an aspiring author finishing his debut novel. Before applying the final touches, he gives the manuscript to his longtime friend, Naomi, on the eve of her life-threatening operation. The manuscript, entitled "The Book of Isabel," is an autobiographical story set in 1999, where Louis first learns to come to grips with lost loves and strained friendships. Taking place in Syracuse and New York City, this story within a story is a continuation of "Hanging Upside Down," that explains Isabel's role in Louis' life and asks the question, do friends really last forever?