Patients complaining of pain or fatigue in the absence of known physical diseases constitute a high percentage of those seeking general medical care. Depending upon the type of physician/specialist consulted, those individuals may receive disease labels that range from an implied psychological origin such as somatoform or psychosomatic disease, or to a presumed physical disease such as fibromyalgia. Although all these conditions are regularly associated with fatigue, we have provided a new label suggesting another disease category, “systemic exertion intolerance disease,” which replaces the previous “chronic fatigue syndrome.” All these conditions have common, overlapping features that usually consist of both fatigue and pain, and, in the absence of definitive objective confirmation, might be best classified under one heading such as somatic symptom disorder. Management of these disorders is challenging, but suggestions for proper identification and treatment are presented.