Modulators of potassium channels are of great interest for their potential scientific as well as clinical value. These agents may be used for a variety of illnesses including asthma, hypertension, myocardial ischemia, and arrhythmias. The development of KATP openers and blockers has opened a large area of research, particularly on their potential role in the pathogenesis of myocardial ischemia. While much work has shown protective effects for KATP openers, it is unknown whether currently existing agents are optimal. It is also possible that KATP openers may be useful for other types of ischemia such as peripheral vascular disease and cerebral ischemia. It would be exciting to develop agents which not only would protect ischemic myocardium, but also reduce the severity of peripheral and cerebral ischemia. The convergence of the KATP opener studies and the preconditioning area of study was a classical intersection of two seemingly independent lines of research. This convergence has been largely responsible for the heightened interest in KATP. Our quest for knowledge on the role of KATP openers in myocardial ischemia and their potential utility has only just begun.