This chapter explores the history of the use of cannabinoids for neuropathic pain, from anecodotal evidence, through the characterization of the endogenous cannabinoid system, to the preclinical and clinical evidence that cannabinoids are therapeutically active for neuropathic pain. With the development of synthetic cannabinoid receptor agonists, antagonists, and knock-out models, a neurophysiological role for cannabinoids in pain modulation began to be explained. The first cannabinoid receptor to be cloned, now called the CB1 receptor, is predominantly found associated with neuronal tissue in both the central and peripheral nervous systems. The chapter reviews the major neuropathic pain syndromes for which there are data from recent epidemiological and clinical studies. The practicing healthcare professional needs to be aware of the cannabinoid system, the existing cannabinoid therapeutic toolbox, and the potential for future developments (both scientific and regulatory) of cannabinoid medications.