Asthenia is a clinical syndrome that can be manifest in almost all somatic, infectious, and neurological diseases. Initially a protective mechanism indicating depletion of energy resources, asthenia can become a pathological and extremely disabling condition, and can even progress to an independent immune-mediated disease - chronic fatigue syndrome. Asthenia is often combined with affective and cognitive disorders, producing diagnostic difficulties. The article addresses the complex interweaving of asthenia, chronic fatigue syndrome, and cognitive and affective disorders.