The International Association for the Study of Pain defines pain as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. A good understanding of the physiology of pain processing is important, with recent advances in basic science, functional neuroimaging, and clinical pain syndromes contributing to our understanding. It is also important to differentiate between nociception, the process of detecting noxious stimuli, and pain perception, which is a much more complex process, integrating biological, psychological, and social factors. The somatosensory nervous system, from peripheral nociceptors, to sensory nerves and spinal cord synapses has many potential sites for modulation, with ascending pathways to the brain, balanced by ‘top-down’ control from higher centres. Under certain circumstances, for example, after tissue injury from trauma or surgery, there will be continued nociceptive input, with resultant changes in the whole somatosensory nervous system that lead to development of chronic pain syndromes. In such cases, even when the original injury has healed, the pathophysiological changes in the nervous system itself lead to ongoing pain, with peripheral or central sensitization, or both. Additionally, in some chronic pain syndromes, for example, chronic widespread pain, it has been postulated that abnormalities in central processing may be the initiating factor, with some evidence for this from neuroimaging studies. Further work is needed to fully understand pain neurobiology in order to advance our management.