AbstractIn contrast to physiological pain, pathological pain is not dependent on the presence of tissue‐damaging stimuli. One type of pathological pain—neuropathic pain—is often a consequence of nerve injury or of diseases such as diabetes, AIDS, or cancer. Neuropathic pain can be agonizing, can persist over long periods, and, unfortunately, is often resistant to known painkillers. There is a rapidly growing body of evidence indicating that microglia, the CNS immune cells, have causal roles in the pathogenesis of pain hypersensitivity following nerve injury. We will review recent advances in our understanding of the mechanisms producing neuropathic pain, focusing on the roles of microglia‐expressed molecules, including cell surface receptors, intracellular signaling molecules, and diffusible factors involved in nerve injury‐induced pain behaviors and hyperexcitability of dorsal horn neurons. Elucidating how spinal microglia cause neuropathic pain may provide us with exciting insights into pain mechanisms and clues for developing new drugs for the treatment of neuropathic pain. © 2009 Wiley‐Liss, Inc.