Prolongation of the cardiac action potential duration is the hallmark of Class III antiarrhythmic activity. Action potential duration prolongation may be achieved by several means: enhancement of inward current and, more commonly, blockade of one or more of the many outward currents that are carried by K+. However, it is far from clear whether blockade of one particular K+ channel is more efficacious than blockade of another. The objective of this review is to consider this question with particular reference to ischaemic heart disease, a condition for which effective prevention of ventricular arrhythmias continues to be sought.