Organ transplantation is the standard treatment modality for end-stage organ disease in selected cases. Two types of potential organ donors can be identified: the brain-dead 'heart-beating donors', referred to as DBD (donation after brain death), and the warm ischaemic 'non-heart-beating donors', referred to as DCD (donation after circulatory death). Brain death induces several physiological changes in the DBD donor. An autonomic storm is characterized by massive catecholamine release, followed by autonomic depletion during a vasoplegic phase. This is associated with several hormonal changes (suppression of vasopressin, the hypothalamic-pituitary-adrenal axis, and the hypothalamic-pituitary-thyroid axis) and an inflammatory response. These physiological changes form the basis of organ donor management, including cardiovascular stabilization and hormonal therapy (including vasopressin and analogues, thyroid hormone, and cortisol). Donor management is the continuation of critical care, with a shift towards individual organ stabilization. An aggressive approach to maximize organ yield is recommended; however, many treatment strategies need further investigation in large randomized trials. DCD donors have now evolved as a valid alternative to increase the potential donor pool and challenge the clinician with new questions. Optimal donor comfort therapy and end-of-life care are important to minimize the agonal phase. A strict approach towards the determination of death, based on cardiorespiratory criteria, is prerequisite. Novel strategies have been developed, using ex situ organ perfusion as a tool, to evaluate and recondition donor organs. They might become more important in the future to further optimize organ quality.