For patients with ischaemic heart disease, remote ischaemic conditioning may offer an innovative, non-invasive and virtually cost-free therapy for protecting the myocardium against the detrimental effects of acute ischaemia-reperfusion injury, preserving cardiac function and improving clinical outcomes. The intriguing phenomenon of remote ischaemic conditioning was first discovered over 20 years ago, when it was shown that the heart could be rendered resistant to acute ischaemia-reperfusion injury by applying one or more cycles of brief ischaemia and reperfusion to an organ or tissue away from the heart – initially termed ‘cardioprotection at a distance’. Subsequent pre-clinical and then clinical studies made the important discovery that remote ischaemic conditioning could be elicited non-invasively, by inducing brief ischaemia and reperfusion to the upper or lower limb using a cuff. The actual mechanism underlying remote ischaemic conditioning cardioprotection remains unclear, although a neuro-hormonal pathway has been implicated. Since its initial discovery in 1993, the first proof-of-concept clinical studies of remote ischaemic conditioning followed in 2006, and now multicentre clinical outcome studies are underway. In this review article, we explore the potential mechanisms underlying this academic curiosity, and assess the success of its application in the clinical setting.