Chronic pain is the most difficult type of pain to treat. Previously, the development of analgesics has focused on neuronal targets; however, current analgesics are only modestly effective, have significant side effects and do not provide universal efficacy. New strategies are needed for the development of more effective analgesics. Glial cells have integral roles in CNS homeostasis, and chronic pain etiology and progression. In this review, the role of glia in neuropathic pain and opioid administration is described, as well as the potential superior efficacy and wider therapeutic indices provided by drugs that modulate specific glial function via novel targets.