Electrochemical homeostasis, sound transduction and auditory neurotransmission in the cochlea are influenced by extracellular purines and pyrimidines. 2. Evidence that ATP and related nucleotides influence inner ear function arises from a considerable number of cellular, molecular and physiological studies in vitro and in vivo. 3. With a full understanding of these processes, which include ionotropic (P2X receptor) and metabotropic (P2Y receptor) signal transduction pathways, signal termination involving ecto-nucleotidases and recycling via nucleoside transporters, exciting possibilities emerge for treating hearing disorders, such as Meniere's disease, tinnitus and sensorineural deafness.