Knowledge in neuropathic pain has grown rapidly during the past few years. Central and peripheral sensitization is still believed to be the main pathophysiology. New evidence suggests many potential new molecular targets and mechanisms, such as cytokines, lysophosphatidic acid and ion channels. Microglia and astrocyte activation leads to dysregulation of inflammatory cytokines and pain signaling. Many subtypes of the sodium channel have been shown to be the culprit for both congenital and acquired pain syndromes, especially small fiber neuropathy. Lysophosphatidic acid is thought to act as an initiator of neuropathic pain, along with other mediators. Animal models of neurodegenerative diseases and chemotherapy-induced neuropathy reaffi rm the role of nociceptor degeneration and cytoskeletal breakdown in peripheral neuropathy. With better understanding of its mechanism, it may lead to new therapeutic targets. Recent trials of new medications, new formulations or new indication of old drugs have shown promising data. We can look forward to better treatment of this debilitating symptom in the near future.