Cancer-related fatigue is a common and distressing symptom that is present in the majority of cancer patients at some point during the disease course. Cancer-related fatigue has a profound influence on patients, affecting functional performance, mood, and one's overall quality of life. The etiology of cancer-related fatigue is multifactorial, involving a complex interplay of biological and body system factors. All cancer patients should be screened for fatigue, as it often coexists with other symptoms and its side effects may be underdiagnosed. Treatment modalities for cancer-related fatigue are still evolving. Current recommendations for management from national and international cancer experts and societies focus on patient and family education regarding cancer-related fatigue, exercise and physical activity, and psychosocial interventions. Pharmacologic interventions are less effective but may be helpful in a selected subset of affected individuals.