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Heart transplantation (HTx) outcomes have improved with careful donor selection and management; nonetheless, donor shortages remain a major challenge. Optimizing donor management is crucial for improving donor utility rates and post-HTx outcomes. Brain death leads to various pathophysiological changes that can affect multiple organs, including the heart. Understanding these alterations and corresponding management strategies is key to optimizing the donor organ condition. This review assesses several aspects of these pathophysiological changes, including hemodynamic and endocrinological considerations, and emphasizes special consideration for potential cardiac donors, including serial echocardiographic evaluations for reversible cardiac dysfunction and coronary assessments for donors with risk factors.