Acid Sensing Ion Channels (ASICs) are a family of cation channels expressed principally in neurons and that are activated by protons. The sensitivity of ASICs to acidosis and their distribution in primary sensory neurons points to a significant role of these channels in acid nociception. However, despite the fact that the first ASIC was identified more than 10 years ago the physiological and pathophysiological role of this channel family remains poorly understood. In this paper, the available body of data (genetic, pharmacological, and other) on ASICs will be reviewed and the role of ASIC in normal nociception and other pain sensations will be discussed. Some of the recent drug discovery and development activities ongoing in our laboratory, which point to ASICs being a relevant target for pain modulation, will also be summarized.