Background and Objectives: Cachexia is a paraneoplastic syndrome that affects the large majority of patients with end-stage cancer. No known therapy exists to effectively overcome the severe symptoms of cachexia, which include anorexia, weight loss and fatigue. This study considered the results of both experimental and clinical studies to evaluate the suitability of L-carnitine and its derivatives as potential therapies for cachexia in patients with cancer. Methods and Study Design: All available English-language papers on the use of L-carnitine in pa- tients with cachexia related to cancer, including reviews, case reports, case series, and clinical trials, were ob- tained by searching multiple databases, including all Elsevier publications, Web of Knowledge, PubMed, Scopus, clinical trials, and the Cochrane database of systematic reviews. Results: The protective effects of L-carnitine were extracted from the literature review based on critical mechanisms involved in skeletal muscle loss, including increased proteolysis, impaired protein synthesis, myonuclear apoptosis, oxidative stress, and mitochondrial dys- function. The results of this process favored L-carnitine supplementation in patients with cancer-related cachexia. Nitrogen balance was improved either through the increase of protein synthesis or by reduction in proteolysis, in- hibiting apoptosis or reversing inflammatory processes. Conclusions: Although clinical studies are inconclusive, studies in animal models support L-carnitine administration to prevent oxidative stress and ameliorate mitochon- drial function. L-carnitine supplementation leads to beneficial effects on several critical mechanisms involved in pathologic skeletal muscle loss and improved fatigue-related parameters in patients with cancer. However, more well-designed, double-blinded, randomized clinical trials are necessary to establish L-carnitine supplementation as a therapeutic strategy for cachexia.