Effective protection against the consequences of transient myocardial ischaemia requires a consideration of events not only during the ischaemic interval but also during the pre- and post-ischaemic periods. Thus, the promotion of maximal energy reserves and the reduction of catecholamine drive before ischaemia are likely to increase tissue resistance. Similarly, limitation of various reperfusion effects such as cell swelling, energy over-demand or calcium over-load may improve either the rate or extent of post-ischaemic recovery. Although pre- and post-ischaemic conditioning are little studied, protection during ischaemia has been extensively investigated and, in the case of surgically-induced ischaemia, has been shown to be highly effective. Thus, the introduction of cold chemical cardioplegia to routine cardiac surgery has allowed the tolerable duration of ischaemia to be extended from less than 1 to more than 3 hours and in experimental studies up to 24 hours of reversible ischaemia has been reported. Three components of effective protection can be defined: (i) conservation of energy by inducing instantaneous arrest with agents such as potassium; (ii) slowing the metabolic rate of energy consuming and degradative reactions with hypothermia; (iii) combating deleterious ischaemia-induced changes with specific protective agents. Analysis of the principles underlying these three components and the mechanisms of action of specific interventions, reveals the control of calcium movement to be one of the most critical factors in effective myocardial protection. The principles underlying cold chemical cardioplegia and protection of the myocardium during cardiac surgery are reviewed and future advances in this field discussed.