Fatigue is the most commonly reported symptom in cancer patients and has a profound effect on patient quality of life (QOL). The Fatigue-1 and Fatigue-2 surveys performed by the Fatigue Coalition have shown that fatigue occurs on a consistent basis in approximately three quarters of patients treated for cancer. Fatigue-2 study results show that fatigue is associated with significant physical, emotional, psychologic, and social consequences, with virtually every aspect of daily life being affected. Patients also report that fatigue interferes with both their own and their caregivers' careers and economic status. Fatigue-2 documented a significant communication gap between patient and physician regarding fatigue and nonspecific physician responses to patient reports. This finding suggests that patients may benefit from physician initiation of discussion of the causes and treatments of fatigue and from physician education regarding available treatment modalities. Additional research is needed to elucidate the nature of fatigue in cancer patients. Algorithms for the differential diagnosis and treatment of cancer fatigue need to be developed and implemented to assist in timely recognition and management.