Prurigo nodularis (PN) is a chronic, highly pruritic condition characterized by the presence of hyperkeratotic, excoriated, pruritic papules and nodules, with a tendency to symmetrical distribution. No reliable data exist about incidence and prevalence of PN in the general population, but it seems to be more frequent and more intense in females. PN may be associated with many dermatological and non-dermatological comorbidities, including psychiatric disease. Recent findings suggest a neuropathic origin of PN, with alterations in the dermal and epidermal small diameter nerve fibers. PN may have a tremendous impact on the quality of life, and few effective treatment options are available. Few randomized controlled trials (RCT) on the therapy of PN are available, demonstrating the efficacy of phototherapy alone or with psoralen, and of topical calcipotriol and topical steroids in occlusive medications. Thalidomide may be effective, but no RCT are available and its use is impractical due to the unfavorable safety profile. Gabapentin, pregabalin and the neurokinin receptor 1 antagonist, aprepitant, seem also to be effective in the therapy of PN, but RCTs are still lacking.