Machine perfusion (MP) is at the forefront of innovation in modern liver transplantation. Several approaches, mainly varying the temperature at which the graft is perfused, have shown benefit in preclinical models and nonrandomized clinical trials. Given the recent randomized controlled trial by Nasralla et al demonstrating the efficacy of normothermic MP over static cold storage, MP is likely here to stay for the foreseeable future. We are only beginning to explore the possibilities of this technology, including the prediction of graft function and modification of suboptimal livers. This has the potential to both increase the donor pool and improve the quality of grafts provided to recipients. Beyond transplantation, there may be a role for MP in extracorporeal liver support, cancer research and therapeutics, and pharmaceutical testing. In this review, we provide the rationale and explore the relevant preclinical studies that support the use of ex situ liver perfusion for these extended applications.