Cancer-related fatigue (CRF) significantly interferes with usual functioning because of the distressing sense of physical, emotional, and cognitive exhaustion. Assessment of CRF is important and should be performed during the initial cancer diagnosis, throughout cancer treatment, and after treatment using a fatigue scoring scale (mild-severe). The general approach to CRF management applies to cancer survivors at all fatigue levels and includes education, counseling, and other strategies. Nonpharmacologic interventions include psychosocial interventions, exercise, yoga, physically based therapy, dietary management, and sleep therapy. Pharmacologic interventions include psychostimulants. Antidepressants may also benefit when CRF is accompanied by depression.