We have seen huge progress in our understanding as to how sensory neurons detect tissue injury and transmit this information to the central nervous system. This is critically dependent on a repertoire of ligand gated ion channels responding to thermal, mechanical and chemical stimuli and voltage gated ion channels which set excitability and are required for the generation of action potentials. Genetic variants in these same ion channels can lead to human Mendelian pain disorders which include the phenotypic extremes of both loss of pain and enhanced pain. The distinct clinical phenotypes can be related to the biophysical changes in channel function. We also recognise that variants in these same channels may contribute to the risk of more common acquired neuropathic pain disorders and pain perception at a population level. This knowledge has highlighted new analgesic drug targets and the development of new treatments as well as a more personalised pain medicine approach.