Ischaemic preconditioning can be defined as the protective adaptive mechanism produced by short periods of ischaemic stress resulting in a marked, albeit temporary, resistance of the myocardium to a subsequent more prolonged period of that same stress. This protection includes reductions in ischaemic cellular damage and in life-threatening ventricular arrhythmias. The most likely mechanisms for this protection are discussed in this review by James Parratt and involve the release of endogenous substances from the ischaemic myocardium (for example, adenosine, bradykinin, nitric oxide and prostacyclin) with the possible involvement of ATP-dependent K+ channels, Gi proteins and protein kinase C. If we understood more fully the precise mechanisms of this pronounced protection, it should be possible to exploit them pharmacologically to ultimate therapeutic advantage.