CONTEXT: Cancer-related fatigue (CRF) is a common and distressing symptom affecting patients with cancer. There is an increasing number of drug trials examining potential treatments for CRF. Methylphenidate represents one of the most researched drugs in this area, and an up-to-date assessment of the evidence for its use is needed. OBJECTIVES: To assess and summarize the increasing evidence for the use of psychostimulants, particularly methylphenidate, in the treatment of CRF. METHODS: A systematic review of electronic databases was conducted from inception to the start of October 2009, together with cross-referencing of cited abstracts and hand searching of relevant cancer journals. RESULTS: A meta-analysis was conducted on five psychostimulant trials (n=426 participants). The overall standardized mean difference was -0.28 (95% confidence interval [CI] -0.48, -0.09; P=0.005), although several trials failed to find any benefit over placebo. There were no differences in the frequency of adverse events between methylphenidate and placebo: combined odds ratio 1.24 (95% CI 0.42, 3.62). CONCLUSION: There is preliminary evidence for the use of psychostimulants to treat CRF. The absolute numbers still remain small, and further confirmation is needed before firm recommendations on their usage and safety can be made in the treatment of CRF.