AbstractRyanodine receptors (RyR) are cation‐selective, ligand‐modulated, ion channels that provide a pathway for the regulated release of Ca2+from intracellular reticular storage organelles to initiate a wide variety of cellular processes. In addition to regulation by endogenous ligands, the function of RyR can be altered by many pharmacological agents. Some of these have been used to establish the contribution of RyR‐mediated Ca2+release to diverse signaling processes. Altered RyR function also plays a role in the development of diseases of both skeletal and cardiac muscles, hence both new and established compounds have potential as RyR‐focussed therapeutic agents.WIREs Membr Transp Signal2012, 1:383–397. doi: 10.1002/wmts.34For further resources related to this article, please visit theWIREs website.