PURPOSE: Cancer-related fatigue contributes to negative outcomes relative to psychosocial and symptom distress, functional status, and quality of life, and yet it is often underdiagnosed and management is frequently suboptimal. DESIGN: Systematic database searches were conducted, and primary research reports and meta-analyses of quantitative studies of interventions for fatigue published in English were identified and critically examined. RESULTS: This paper reviews the etiology and evaluation of cancer-related fatigue and analyzes current empirical evidence supporting pharmacologic and nonpharmacologic techniques for its management. DISCUSSION: A variety of pharmacologic and nonpharmacologic techniques to manage cancer-related fatigue have been studied, although most of the evidence is from single-arm pilot studies with small sample sizes, rather than from adequately powered, multicenter, randomized controlled trials. Continued research in ethnically and racially diverse samples is needed to identify the interventions that are most effective in specific cancer subpopulations and to develop and test interventions for fatigue at each phase in the illness trajectory.