The chronic fatigue syndrome is an illness of unknown etiology characterized by severe fatigue, myalgias, lymphadenopathy, arthralgias, chills, fevers, and postexertional malaise. Recognizing chronic fatigue syndrome is primarily a method of exclusion with no definitive diagnostic test or physical findings. As research continues to delve into the many possible etiologic agents for chronic fatigue syndrome-infectious, immunologic, neurologic, or psychiatric alone or in combination- the answer remains elusive. What is known is that chronic fatigue syndrome is a heterogeneous disorder very possibly involving an interaction of biological systems. Therefore, chronic fatigue syndrome may describe a large subset of patients, each exhibiting unique symptoms and serologic profiles dependent on the nature of the onset of illness and the genetic profile of individual patients.