This review focuses on the application of hypothermic perfusion technology as a topic of current interest with the potential to have a salutary impact on the mounting clinical challenges to improve the quantity and quality of donor organs and the outcome of transplantation. The ex vivo perfusion of donor organs on a machine prior to transplant, as opposed to static cold storage on ice, is not a new idea but is being re-visited because of the prospects of making available more and better organs for transplantation. The rationale for pursuing perfusion technology will be discussed in relation to emerging data on clinical outcomes and economic benefits for kidney transplantation. Reference will also be made to on-going research using other organs with special emphasis on the pancreas for both segmental pancreas and isolated islet transplantation. Anticipated and emerging benefits of hypothermic machine perfusion of organs are: i) maintaining the patency of the vascular bed, ii) providing nutrients and low demand oxygen to support reduced energy demands, iii) removal of metabolic by-products and toxins, iv) provision of access for administration of cytoprotective agents and/or immunomodulatory drugs, v) increase of available assays for organ viability assessment and tissue matching, vi) facilitation of a change from emergency to elective scheduled surgery with reduced costs and improved outcomes, vii) improved clinical outcomes as demonstrated by reduced PNF and DGF parameters, viii) improved stabilization or rescue of ECD kidneys or organs from NHBD that increase the size of the donor pool, ix) significant economic benefit for the transplant centers and reduced health care costs, and x) provision of a technology for ex vivo use of non-transplanted human organs for pharmaceutical development research.