Cardiac myosin binding protein-C (cMyBP-C) is a cardiac-specific thick filament assembly, accessory and regulatory protein. Physiologically, it is a key regulator of cardiac contractility. With more than two hundred mutations in the cMyBP-C gene directly linked to the development of cardiomyopathy and heart failure, cMyBP-C clearly plays a critical role in heart function. At baseline, cMyBP-C is highly phosphorylated, a condition required for normal cardiac function. However, the level of cMyBP-C phosphorylation is significantly decreased during heart failure, indicating that the level of cMyBP-C phosphorylation is directly linked to signaling and cardiac function. Early studies indicated that cMyBP-C interacts with myosin and titin, whereas studies now show that it also interacts with thin filament proteins. However, the exact role(s) of cMyBP-C in the heart remain(s) to be elucidated. As such, we invited experts in the field of cardiac muscle to identify and address key issues related to cMyBP-C by contributing a mini-review on such topics as structure, function, regulation, cardiomyopathy, proteolysis, and gene therapy. Starting from this issue, Pflügers Archiv European Journal of Physiology will publish two invited mini-review articles each month to discuss the most recent advances in the study of cMyBP-C.