This aim of this systematic review was to determine the prevalence and pattern of cancer-related fatigue (CRF), and identify factors associated with its development. Relevant literature was identified through an electronic database search using specified keywords. Included studies investigated CRF in adult cancer patients using a multidimensional fatigue measure. The methodological quality was assessed using six published standards. CRF is apparent both during and after anti-cancer therapy, however, the prevalence of CRF varied between studies. The variables associated with the development and persistence of CRF remain to be identified. Inconsistencies were evident in the pattern of CRF and its associated factors. This is likely to have arisen from the inherent difficulties in the measurement of a subjective sensation, further complicated by the myriad of outcome measures used. More methodologically sound research; assessing CRF from the commencement of therapy, considering all pertinent variables is needed.