A number of high-quality studies have recently been published that examine the association between neuropathic pain and health-related quality of life (HRQoL). The current review identified 52 such studies in patients with six neuropathic pain conditions associated with lesions of either the peripheral (postsurgical neuropathic pain associated with breast and amputation surgery, postherpetic neuralgia, and painful diabetic neuropathy) or central (poststroke pain, spinal cord injury pain, multiple sclerosis pain) nervous system. The results provide strong evidence that the presence and severity of neuropathic pain are associated with greater impairments in a number of important HRQoL domains. However, the evidence also indicates that this impact varies somewhat as a function of the HRQoL domain being considered and that different measures of HRQoL are differentially sensitive to the effects of neuropathic pain. The findings have important implications for the selection of HRQoL domains and measures to use in clinical trials and in clinical research on HRQoL in persons with neuropathic pain and suggest that a biopsychosocial (as opposed to a primarily biomedical) approach would be appropriate for understanding and treating neuropathic pain.