The gate-control-theory of pain attributes a pivotal role in nociceptive processing to inhibitory interneurons in the superficial dorsal horn of the spinal cord. Loss of synaptic inhibition is a contributing factor to the generation and maintenance of chronic pain. Different signaling pathways involved in inflammatory and neuropathic pain converge onto diminished synaptic inhibition in the spinal dorsal horn. Accordingly, restoring inhibition through drugs that facilitate GABAergic or glycinergic neurotransmission should reverse exaggerated pain sensitivity. Indeed, subtype-selective GABAA receptor ligands and inhibitors of glycine transporters might constitute new treatments for chronic pain.