Static cold storage is currently the most used method of organ preservation worldwide. However, cutting edge technology and dramatic changes in the donor pattern have lately renewed the interest toward hypothermic machine perfusion. Marginal and cardiac death donors show higher rates of primary non function and delayed graft function compared to standard criteria donors. In this setting, machine perfusion may offer several theoretical advantages such as improved organ preservation, continuous graft evaluation, and ex-vivo conditioning of the graft before implantation. These topics have been recently reassessed by several studies. In particular, perfusion characteristics (renal resistance) and perfusate biomarker concentrations (lactate dehydrogenase, aspartate aminotransferase, heart-type fatty acid binding protein, and IL-18) during machine preservation, proved to be reliable tools to rule out graft viability and predict outcomes after transplantation. Treatment strategies acting on tissue repair, cell metabolism, and allorecognition pathway are also under investigation with promising results. Machine perfusion has finally shown its real potential however, stronger evidences and updated cost-effectiveness analysis are needed to fully support its role for the next future.