The calcium channel blocker diltiazem lowers heart rate in man and this property probably contributes to its clinical effectiveness in ischaemic heart disease and hypertension. This review examines the pharmacological basis of diltiazem's heart rate-lowering activity and considers its pathophysiological significance. The points discussed include the potent direct inhibitory effect of diltiazem on the sinus node and the frequency-dependence of this action. In addition, the well-balanced tissue selectivity profile of diltiazem and its ability to modulate cardiac reflex responsiveness contribute by counteracting the potential for reflex tachycardia.