Complex regional pain syndrome (CRPS) is a highly painful, limb-confined condition that usually arises after a trauma although its causes remain unknown. It is associated with a particularly poor quality of life, and considerable healthcare and societal costs. Its distinct combination of abnormalities includes limb-confined inflammation and tissue hypoxia, sympathetic dysregulation, small fibre damage, serum autoantibodies, central sensitisation and cortical reorganisation, which place it at the crossroads of disciplines including rheumatology, pain medicine and neurology. The significant scientific and clinical advances made over the past 10 years promise an improved understanding of the causes of CRPS, and for more effective treatments. This review summarises the currently available treatments. The therapeutic approach is multidisciplinary, and involves educating patients about the condition, sustaining or restoring limb function, reducing pain, and providing psychological support. This paper describes the systemic drug treatments, grouped on the basis of their real or presumed antinociceptive mechanisms and reported actions without making any formal distinction between CRPS types I and II.