The development of chronic pain involves increased sensitivity of peripheral nociceptors and elevated neuronal activity in many regions of the central nervous system. Much of these changes are caused by the amplification of nociceptive signals resulting from the modulation and altered expression of specific ion channels and receptors in the central and peripheral nervous system. Understanding the processes by which these ion channels and receptors are regulated and how these mechanisms malfunction may lead to new treatments for chronic pain. Here we review the contribution of the Ca2+-permeable acid-sensing ion channel (ASIC(Ca)) in the development and persistence of chronic pain, and the potential underlying mechanisms. Accumulating evidence suggests that ASIC(Ca) represents an attractive new target for developing effective therapies for chronic pain.