Lumbosacral radiculoplexus neuropathy (LRPN) is a multifocal, asymmetric, painful neuropathic disorder affecting multiple levels of lumbosacral plexus, nerve roots, and distal nerves that emerge from the plexus. The disorder was first described in diabetic patients (DLRPN) and was later found to occur in nondiabetic patients as well. There have been debates as to the pathogenesis of DLRPN and LRPN. Recent detailed and extensive pathologic studies, however, have shown that the main pathogenesis is inflammation and microvasculitis affecting various components in the peripheral nerves, resulting in ischemic injury to the nerves. Even though studies on the natural history of this disorder have shown that the majority of patients recover within a few years after the attack without any treatment (although recovery is incomplete in many cases), it is a common practice, based on the pathophysiology and case series, to administer immunotherapy. Preliminary data from a controlled clinical trial failed to show significant improvement in outcomes measured by neurologic deficits (as judged by the Neuropathy Impairment Score) but did show improvement in symptoms (pain and positive sensory symptoms). Choices of immunotherapy include corticosteroids, intravenous immunoglobulin, plasma exchange, or a combination. Pain management, physical therapy, and treatment of depression remain mainstays for managing this disorder.