Neuropathic pain occurring after peripheral nerve injury is not simply a consequence of temporal continuity of acute nociceptive signals, but rather of maladaptive nervous system function. Over the past decades, a body of literature has provided evidence for the necessity and sufficiency of microglia, the tissue-resident macrophages of the central nervous system, for nerve injury-induced alterations in synaptic function. Recent studies have also revealed active roles for microglia in brain regions important for emotion and memory. In this chapter, I highlight recent advances in our understanding of the mechanisms that underlie the role of spinal and brain microglia in neuropathic pain, with a focus on how microglia are activated and alter synaptic function. I also discuss the therapeutic potential of microglia from recent advances in the development of new drugs targeting microglia, which may facilitate translation from the bench to bedside.