Research over the past two decades has implicated dysfunction of the ryanodine receptor (RyR), a Ca(2+) release channel on the sarcoplasmic reticulum (SR) required for excitation-contraction (EC) coupling, in the pathogenesis of cardiac and skeletal myopathies. These discoveries have led to the development of novel drugs, screening tools, and research methods. The patents associated with these advances tell the story of the initial discovery of RyRs as a target for plant alkaloids, to their central role in cardiac and skeletal muscle excitation-contraction coupling, and ongoing clinical trials with a novel class of drugs called RycalsTM that inhibit pathological intracellular Ca(2+) leak. Additionally, these patents highlight questions, controversies, and future directions of the RyR field.