Calcium (Ca²⁺) is a critical regulator of cardiac myocyte function. Principally, Ca²⁺ is the link between the electrical signals that pervade the heart and contraction of the myocytes to propel blood. In addition, Ca²⁺ controls numerous other myocyte activities, including gene transcription. Cardiac Ca²⁺ signaling essentially relies on a few critical molecular players—ryanodine receptors, voltage-operated Ca²⁺ channels, and Ca²⁺ pumps/transporters. These moieties are responsible for generating Ca²⁺ signals upon cellular depolarization, recovery of Ca²⁺ signals following cellular contraction, and setting basal conditions. Whereas these are the central players underlying cardiac Ca²⁺ fluxes, networks of signaling mechanisms and accessory proteins impart complex regulation on cardiac Ca²⁺ signals. Subtle changes in components of the cardiac Ca²⁺ signaling machinery, albeit through mutation, disease, or chronic alteration of hemodynamic demand, can have profound consequences for the function and phenotype of myocytes. Here, we discuss mechanisms underlying Ca²⁺ signaling in ventricular and atrial myocytes. In particular, we describe the roles and regulation of key participants involved in Ca²⁺ signal generation and reversal.