Fatigue is the most commonly reported symptom in patients with cancer, with a prevalence of over 60% reported in the majority of studies. This paper systematically reviews pharmacologic agents in the treatment of cancer-related fatigue (CRF). We conducted a literature review of clinical trials that assessed pharmacologic agents for the treatment of CRF. These agents include hematopoietics (for anemia), corticosteroids, and psychostimulants. Other therapeutic agents that are less well studied for CRF but are currently the focus of clinical trials include l-carnitine, modafinil, bupropion, and selective serotonin reuptake inhibitors such as paroxetine. Disclosure of potential conflicts of interest is found at the end of this article.