Fatigue, a common complaint of cancer patients, requires a multidisciplinary evaluation and treatment approach because of the multiple etiologies and contributing factors. Current treatments for fatigue include educating patients and caregivers about fatigue, applying etiology-specific treatments, utilizing nonpharmacologic interventions, and prescribing pharmacologic therapies. Often, an individualized treatment plan that includes several modalities may be developed. Presently, there is a lack of well-designed clinical trials to evaluate pharmacologic agents for the treatment of cancer-related fatigue.