This article reviews the effects of changes of heart rate on the ventricular action potential duration. These can be divided into short term (fractions of a second), resulting from the kinetics of recovery of membrane currents, through to long term (up to days), resulting from changes of protein expression. We concentrate on the medium-term changes (time course of the order of 100 s). These medium-term changes occur in isolated tissues and in the intact human heart. They may protect against cardiac arrhythmias. Finally, we discuss the cellular mechanisms responsible for these changes. © 2009 The Physiological Society.