Complex regional pain syndrome (CRPS) is a controversial, ambiguous, and often unreliable concept that presents significant clinical and rating challenges, to the extent that, for any individual case, many of the differential diagnostic issues provide a far more probable explanation of symptoms than does CRPS. The International Association for the Study of Pain (IASP) introduced CRPS in 1994 specifically to replace “reflex sympathetic dystrophy” [RSD] and “causalgia.” The IASP diagnostic protocol for assessing CRPS has led to overdiagnosis, as well as questions regarding the protocol's reliability, validity, and high error rate during field trials. Using the IASP protocol and the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth Edition, the authors discuss the mental health and general medical evaluations that are part of the differential diagnosis of CRPS, which involves both psychological and general medical components. Finally, examiners should be aware that the probability rates for a diagnosis of CRPS following a thorough and extensive differential diagnosis is very small and is further limited by the general lack of scientific credibility for the concept of CRPS. A diagnosis of CRPS in the absence of ruling out all potential differentials is not credible. A sidebar discusses several chapters that are relevant to rating impairment due to causalgia, RSD, and CRPS.