Two-pore domain (K(2P)) channels emerged about a decade ago and since then have been an expanding area of interest. This is because their biophysical and pharmacological properties make them good candidates to support background potassium currents and membrane potential in many cell types. There is clear evidence for TREK-1 and TASK-1 in the heart and these channels are likely to regulate cardiac action potential duration through their regulation by stretch, polyunsaturated fatty acids, pH, and neurotransmitters. TREK-1 may also have a critical role in mediating the vasodilator response of resistance arteries to polyunsaturated fatty acids, thus contributing to their protective effect on the cardiovascular system. TASK-1, on the other hand, is a strong candidate for a role in hypoxic vasoconstriction of pulmonary arteries. Many other members of the K(2P) channel family have been identified in the cardiovascular system, although their functional roles are still to be demonstrated. This review provides an up to date summary of what is known about the involvement of members of the K(2P) channel family in cells of the heart and arterial circulation. Our knowledge of their roles will improve with the rapidly increasing interest in them and as new selective pharmacological tools emerge. As their physiological roles emerge, the K(2P) family of potassium channels may offer promising therapeutic solutions to target cardiovascular diseases.