Neuronal inhibition in nociceptive relay of the spinal cord dorsal horn is essential for the proper processing of nociceptive information. In the spinal cord dorsal horn, the activity of synaptic and extrasynaptic GABAA and glycine receptors generates rapid, Cl(-)-dependent neuronal inhibition. A loss of this ionotropic inhibition, particularly through the collapse of the inhibitory Cl(-) gradient, is a key mechanism by which pathological pain conditions can develop. This review summarizes the roles of ionotropic inhibition in the regulation of nociception, and explores recent evidence that the enhancement of GABAA or glycine receptor activity or inhibitory drive can reverse pathological pain.