Acid-sensing ionic channels (ASICs) are almost ubiquitous in the mammalian nervous system, both at the periphery and in the brain. Strong evidence for the physiological function of these molecules has come from recent knockout experiments. Now it is clear that ASICs are important for certain sensory modalities (mechanoreception and nociception) at the periphery and for learning and memory in the brain. The actual mechanisms by which the acid-gated channels serve these functions remain unclear. The question of whether tissue pH is subject to quick fluctuations of a magnitude sufficient to activate ASICs is a crucial point that will determine the functional significance of these channels.