Fatigue is common among patients presenting to physicians. Fatigue can lead to serious public health consequences and may be caused by a vast array of etiologies. This article reviews the assessment of fatigue from the physical medicine and rehabilitation physician’s perspective. The importance of a history and physical examination is emphasized, complemented by the use of laboratory studies. Rating scales used to assess fatigue from different etiologies are discussed, and patient-friendly Internet resources about fatigue are included.