Members of the ATP-binding cassette (ABC) protein superfamily are integral membrane proteins involved in energy-dependent transport of a wide variety of substrates across biologic membranes. ATP-binding cassette transporters serve as functional barriers against the entry of xenobiotics, for example, in the intestine or at the blood-brain barrier, or contribute to drug excretion, for example, in the kidney or the liver. Many human ABC transporters, such as ABCB1 (P-glycoprotein), ABCC5 (MRP5), or ABCC9 (SUR2), are expressed in the heart, suggesting an important role of these transporters in cardiac drug effects or physiology. Interestingly, mutations in ABCC9, a constituent of cardiac K(ATP) channels, can cause dilated cardiomyopathy in humans, providing evidence that dysfunction of cardiac ABC transporters might have clinical implications. This review aims to give insights into the possible functions of ABC transporters in the heart, their role in drug disposition, as well as control of intracellular cyclic nucleotide levels or regulation of K(ATP) channel conductivity.