Studies seeking to explain mechanisms associated with or causing fatigue are increasing; however, the underlying causes of fatigue remain largely unknown. Thus, identifying and predicting which patients may be at risk for developing fatigue, and tailoring interventions accordingly, are difficult. Whether fatigue experienced by patients with cancer can be classified into specific clinically significant subtypes would be useful to determine. These clinical subtypes might improve understanding of underlying mechanisms and help tailor treatment accordingly. This article refers to fatigue associated with cancer or its treatment as cancer-related fatigue (CRF). Given this broad designation, meant to encompass the array of causal mechanisms and treatment options, the authors recommend that meaningful clinical subtypes be articulated and differentiated. This article therefore reviews CRF definitions and proposes a nonexhaustive set of clinical subtypes that are intended to help sharpen thinking about causality and, ultimately, treatment recommendations.