Background: Different mechanisms are involved in a complex network of interactions resulting in the painful and impairing disorder, complex regional pain syndrome (CRPS). There is convincing evidence that inflammation plays a pivotal role in the pathophysiology of CRPS. Immunomodulating medication reduces the manifestation of inflammation by acting on the mediators of inflammation. Therefore, as inflammation is involved in the pathophysiology of CRPS, immunomodulating medication in CRPS patients may prove beneficial. Objectives: To describe the current empirical evidence for the efficacy of administering the most commonly used immunomodulating medication (ie, glucocorticoids, tumor necrosis factor-a antagonists, thalidomide, bisphosphonates, and immunoglobulins) in CRPS patients. Methods: PubMed was searched for original articles that investigated CRPS and the use of one of the abovementioned immunomodulating agents. Results: The search yielded 39 relevant articles: from these, information on study design, sample size, duration of disease, type and route of medication, primary outcome measures, and results was examined. Discussion: Theoretically, the use of immunomodulating medication could counteract the ongoing inflammation and might be an important step in improving a disabled hand or foot, leading to further recovery. However, more high-quality intervention studies are needed.