This article brings readers up to date with developments in spinal and supraspinal mechanisms in pain. Not long ago, substance P was considered by many to be the pain transmitter in the spinal cord, and descending endogenous modulatory systems were thought to be only inhibitory. The recent past has seen an unprecedented expansion of models for the study of pain mechanisms and, with that, greater understanding of both the complexity and the roles of a variety of endogenous neuroactive substances in pain. It is now well appreciated that the consequences of tissue injury extend far beyond the site of injury and include spinal and supraspinal changes in neuron excitability and activity.