Claire, Rachel, and Allison Barber share the trauma of having lost both parents in a strange and sudden accident. The youngest, Claire, and the oldest, Rachel, also share their late mother's migraine headaches. The novel's focus is Rachel's disappearance and Claire's search for her through North America, Europe, and Mexico. By herself and eventually with the help of Rachel's friend and sometime lover, a massage therapist named Brad Arnarson, Claire traces the steps of Rachel's professional (as a freelance science journalist) and personal meetings with researchers and health practitioners who work on migraines.
Initially, Claire's search is motivated by concern for Rachel and intensified by fears that Rachel's worsening migraines may have caused her to take desperate action. Her need to find Rachel is inevitably intertwined, however, with her own migraine experiences and with her drive to individuate within her family and her longterm relationship with her partner Stefan.
