Fatigue is the most common symptom in patients with advanced cancer. It is a subjective sensation with physical, cognitive, and affective modes of expression. The etiology is often unclear, and multiple potential etiologic factors for fatigue may coexist. Assessing fatigue involves characterizing its severity, temporal features, exacerbating and relieving factors, associated distress, and impact on daily life. Potential factors contributing to fatigue are the cancer itself, cancer treatment, cancer or treatment complications, medications, and other physical and psychosocial conditions. Many fatigue assessment tools exist. Fatigue management involves specific (targeting potentially reversible causes of fatigue) and symptomatic (targeting symptoms because no obvious etiology or reversible cause for fatigue can be identified) intervention and treatment measures. Specific interventions include treating anemia or metabolic and endocrine abnormalities, as well as managing pain, insomnia, depression, and anxiety. Symptomatic treatment involves education, counseling, and pharmacologic, and nonpharmacologic measures. Pharmacologic agents that have been investigated for use in treating fatigue include corticosteroids, progestational agents, and psychostimulants. Agents that modulate cytokine activity are future treatment possibilities.