Neuropathic pain (NP), caused by a primary lesion or dysfunction in the nervous system, affects approximately 4 million people in the United States each year. It is associated with many diseases, including diabetic peripheral neuropathy, postherpetic neuralgia, human immunodeficiency virus-related disorders, and chronic radiculopathy. Major pathophysiological mechanisms include peripheral sensitization, sympathetic activation, disinhibition, and central sensitization. Unlike most acute pain conditions, NP is extremely difficult to treat successfully with conventional analgesics. This article introduces a contemporary management approach, that is, one that incorporates nonpharmacological, pharmacological, and interventional strategies. Some nonpharmacological management strategies include patient education, physical rehabilitation, psychological techniques, and complementary medicine. Pharmacological strategies include the use of first-line agents that have been supported by randomized controlled trials. Finally, referral to a pain specialist may be indicated for additional assessment, interventional techniques, and rehabilitation. Integrating a comprehensive approach to NP gives the primary care physician and patient the greatest chance for success.