The long-term preservation of organ explants and protection from cold ischaemia and subsequent rewarming reperfusion injury is essential to successful allografting and instrumental in enlarging the international donor pool. Current hypothermic preservation solutions may have reached the limit of what is possible in terms of explant longevity and viability, and research attention has been turned to novel organoprotective pharmacotherapeutics that could provide the next generation of explant/transplant nurture. Organoprotection is equally paramount during surgical procedures requiring a period of ischaemia as in coronary artery bypass grafting, angioplasty or stenting. Similarly, the phenomenon of non-freezing cold injury (NFCI), associated with microcirculatory and neuronal damage in exposed and often immersed extremities, also involves ischaemia–reperfusion injury. Whilst additions to cold storage solutions of antioxidants and modulators of cellular metabolism may extend their preservative efficacy, pharmacological triggers of ischaemic preconditioning and the hibernation phenotype may offer breakthroughs in the prevention of ischaemia–reperfusion injury.