The treatment of chronic inflammatory and neuropathic pain is a major concern, and the need for new more effective analgesics with less adverse effects is immense. Traditionally, mechanisms proposed for pain modulation have centered almost exclusively on peripheral or central neurons in the pain pathways. Recent research, however, indicates that activation of microglia and astrocytes in the dorsal horn of the spinal cord is of central importance for the development of chronic pain states. Understanding the intercellular communication among astrocytes, microglia, and neurons in the dorsal horn during acute and chronic pain may be instrumental for the development of new analgesic drugs. The purpose of this review is to highlight the role of astrocytes in regulating pain processing.