Ischaemic preconditioning (IPC), also known as ischaemic tolerance (IT), is a phenomenon whereby tissue is exposed to a brief, sublethal period of ischaemia, which activates endogenous protective mechanisms, thereby reducing cellular injury that may be caused by subsequent lethal ischaemic events. The first description of this phenomenon was in the heart, which was reported by Murry and co-workers in 1986. Subsequent studies demonstrated IPC in lung, kidney and liver tissue, whereas more recent studies have concentrated on the brain. The cellular mechanisms underlying the beneficial effects of IPC remain largely unknown. This phenomenon, which has been demonstrated by using various injury paradigms in both cultured neurons and animal brain tissue, may be utilised to identify and characterise therapeutic targets for small-molecule, antibody, or protein intervention. This review will examine the experimental evidence demonstrating the phenomenon termed IPC in models of cerebral ischaemia, the cellular mechanisms that may be involved and the therapeutic implications of these findings.