Complex regional pain syndrome (CRPS) remains a troubling and often refractory pain condition for which the existing treatments are inadequate. The review by Niesters et al in this journal highlights the interesting findings of several recent studies of the NMDA receptor antagonist ketamine in the treatment of CRPS. These studies report a robust analgesic effect that outlasts the period of infusion by weeks. However set against these positive findings are the issues presented by Ketamine pharmacokinetics, side effects and also the observation that these analgesic benefits are not mirrored by improvements in function or affect. In this commentary we consider the wider perspective of the potential for developing and evaluating this sort of NMDA antagonist therapy for the long-term management of CRPS patients.