Despite being a recognized clinical entity for over 140 years, complex regional pain syndrome (CRPS) remains a difficult-to-treat condition. While there have been multiple therapies explored in the treatment of CRPS, NMDA antagonists such as ketamine continue to hold significant interest because of their potential ability to alter the central sensitization noted in chronic pain states. The objective of this review is to identify published literature for evidence of the efficacy and safety of ketamine in the treatment of CRPS. PubMed and the Cochrane Controlled Trials Register were searched (final search 26 May 2011) using the MeSH terms 'ketamine', 'complex regional pain syndrome', 'analgesia' and 'pain' in the English literature. The manuscript bibliographies were then reviewed to identify additional relevant papers. Observational trials were evaluated using the Agency for Healthcare Research and Quality criteria; randomized trials were evaluated using the methodological assessment of randomized clinical trials. The search methodology yielded three randomized, placebo-controlled trials, seven observational studies and nine case studies/reports. In aggregate, the data available reveal ketamine as a promising treatment for CRPS. The optimum dose, route and timing of administration remain to be determined. Randomized controlled trials are needed to establish the efficacy and safety of ketamine and to determine its long-term benefit in CRPS.