Neuropathic pain is a clinical entity that presents unique diagnostic and therapeutic challenges. This chapter addresses the classification, epidemiology, pathophysiology, diagnosis, and treatment of neuropathic pain syndrome. Neuropathic pain can be distinguished from nociceptive pain based on clinical signs and symptoms. Although neuropathic pain presents a significant burden to individuals and society, a more accurate assessment of resource utilization, costs, and impairments associated with neuropathic pain would facilitate appropriate planning of healthcare policies. The underlying pathophysiology of neuropathic pain is not well defined. Several theories regarding the mechanism of neuropathic pain have been proposed, including central and peripheral nervous system sensitization, deafferentation, neurogenic inflammation, and the wind up theory. Neuropathic pain is a clinical diagnosis and requires a systematic approach to assessment, including a detailed history, physical examination, and appropriate diagnostic testing. The mainstay of treatment for neuropathic pain is pharmacological, including the use of antidepressants, antiepileptics, topical anesthetics, and opioids. Nonpharmacological treatments include psychological approaches, physical therapy, interventional therapy, spinal cord stimulation, and surgical procedures. Neuropathic pain is difficult to treat, but a combination of therapies may be more effective than monotherapy. Clinical practice guidelines provide an evidence-based approach to the treatment of neuropathic pain.