After some early hints, cotransmission was proposed in 1976 and the 'chemical coding' gradually established for sympathetic, parasympathetic, sensory-motor, enteric and some invertebrate nerves. More recently, cotransmission has been recognised in the central nervous system. ATP appears to be a primitive signalling molecule that has been retained as a cotransmitter in every nerve type in both peripheral and central nervous systems, although the relative role of ATP varies considerably in different species and pathological conditions. In the past two years, interest has focused on the mechanisms underlying cotransmission, plasticity and differential control of cotransmitter expression.