CFS and FM are clinical conditions characterized by a variety of nonspecific symptoms including prominent fatigue, myalgia, and sleep disturbances. There are no diagnostic studies or widely accepted, pathogenic, explanatory models for either illness. Despite remarkably different diagnostic criteria, CFS and FM have many demographic and clinical similarities. More specifically, few differences exist in the domains of symptoms, examination findings, laboratory tests, functional status, psychosocial features, and psychiatric disorders. FM appears to represent an additional burden of suffering among those with CFS, however, underscoring the importance of recognizing concurrent CFS and FM. Further clarification of the similarities (and differences) between CFS and FM may be useful in studies of prognosis and help define subsets of patients who may benefit from specific therapeutic interventions.