Changes of intracellular Ca2+ concentration regulate many aspects of cardiac myocyte function. About 99% of the cytoplasmic calcium in cardiac myocytes is bound to buffers and their properties will therefore have a major influence on Ca2+ signalling. This article considers the fundamental properties and identities of the buffers and how to measure them. It reviews the effects of buffering on the systolic Ca2+ transient and how this may change physiologically as well as in heart failure and both atrial and ventricular arrhythmias. It is concluded that the consequences of this strong buffering may be more significant than currently appreciated and a fuller understanding is needed for proper understanding of cardiac calcium cycling and contractility.