Cancer-related fatigue (CRF) is a disabling and distressing symptom that is 
highly prevalent across the cancer continuum from a patient's diagnosis and 
treatment through survivorship and end of life. It has a multifactorial etiology 
and significant individual variability in its clinical expression, determinants, 
and sequelae. Despite the significance of CRF, it is often underdiagnosed, and 
management is frequently suboptimal. This review synthesizes the state of the 
science concerning the features, possible mechanisms, and predictors of CRF; 
offers recommendations for the evaluation of CRF; and appraises the strength of 
the evidence for a wide range of pharmacologic and nonpharmacologic 
interventions to prevent and manage fatigue during and after cancer and its 
treatment. There is evidence from methodologically rigorous controlled trials 
that exercise, psycho-educational interventions, and cognitive-behavioral 
therapy for insomnia are effective in the treatment of CRF, and a wide range of 
pharmacologic and nonpharmacologic interventions has shown initial promise in 
single-arm pilot studies with small, heterogeneous samples. Rigorously designed 
and adequately powered randomized trials are warranted to (1) determine the 
effectiveness of promising approaches and (2) identify the interventions that 
are most effective in treating CRF in specific subpopulations (eg, stem cell 
transplant recipients, older adults, patients with lung or colorectal cancers, 
survivors, and those at the end of life). Studies to elucidate the biologic 
expression profiles of CRF, to explicate the mechanisms through which particular 
interventions impact CRF, and to identify the mediators and moderators of 
fatigue outcomes will ultimately permit individually tailored approaches for the 
treatment of CRF.