The widening gap between supply and demand for liver transplantation has prompted many transplant centers to use donors after cardiac death or non-heart-beating donors. These livers - contrary to "classical" brain-dead donors - are exposed to an unavoidable period of warm ischemia, jeopardizing graft function post-transplantation. In a newly developed preclinical model of liver transplantation, we studied - in a biologically unmodified environment - the exact tolerance of the liver to warm ischemia. Following the evidence that liver transplantation from non-heart-beating donors is feasible and safe, provided that warm and cold ischemia are kept short, a clinical programme of liver transplantation from non-heart-beating donors was successfully initiated in our and other Belgian centers. Recently, we demonstrated that the tolerance of such livers to warm ischemia could be substantially improved when some of the previously identified mechanisms leading to graft non-function were tackled by a multi-factorial pharmacological strategy. Meanwhile, cold storage has proven to be insufficient to optimally preserve organs from non-heart-beating donors. As an alternative, machine perfusion preservation was found to consistently improve outcome in kidney transplantation from non-heart-beating donors. Similarly, machine perfusion preservation could improve the preservation of livers, allowing to predict viability prior to transplantation and to ameliorate tolerance to warm ischemia. At present, the definition and development of optimal machine perfusion settings are under investigation at our institution.