All explanatory models of the causes and mechanisms of fatigue and exhaustion proceed from the assumption of a complex, multi factorial process. The causes and mechanisms of CRF may be associated with the tumor itself or with its treatment, or indeed with a potential genetic predisposition, an accompanying physical or mental illness, or behavioral and environmental factors (14, 15). Thus, a wide range of possible causes and influences—somatic, affective, cognitive, and psychosocial—that often cannot easily be separated from one another share cancer-related fatigue as a final common pathway. The following underlying pathophysiological factors are discussed in the literatur