Heart transplantation remains the definitive treatment for end-stage heart diseases. The rising demand for heart transplants underscores the need to expand the donor pool by using marginal and long-distant donors with the potential of increasing the rate of primary graft dysfunction. On-going ischemia under static cold storage (SCS) contributes to myocardial injury, severe primary graft dysfunction, and increased mortality, highlighting the necessity for improved graft preservation strategies. Hypothermic oxygenated machine perfusion (HOPE) offers a promising solution by continuously delivering oxygenated, nutrient-rich cardioplegic fluid under hypothermic conditions. This chapter will review the pre-clinical and clinic studies using HOPE to preserve donor hearts for transplantation. Mechanistic studies demonstrates that HOPE increases ischemia tolerance by enhancing succinate clearance, preserving ATP levels, and minimizing free radical formation. Pre-clinical and clinical studies have reinforced HOPE’s potential to attenuate tissue injury and reduce primary graft dysfunction. Initial clinical studies suggest that HOPE is safe and has favorable impact on heart transplant outcomes. Despite the promising outcomes, most existing clinical studies on HOPE are limited by small sample sizes and a lack of randomization, which could affect the generalizability of the results. Future research should focus on conducting larger, randomized controlled trials to provide more robust evidence on the efficacy and safety of HOPE. Furthermore, future integration of HOPE with innovative technologies such as real-time monitoring of tissue metabolism, pharmacologic or biological modifications of the donor heart during HOPE may lead to better outcomes.