“Nothing is no longer certain than death”, as a very famous proverb claims. In fact, behind this seemingly simple and banal sentence, many theoretical and practical questions are hidden. We are biological beings and while the finality of human life is indisputable, the way to design and define ‘eternal rest’ has changed over time, as if, with the development of scientific knowledge and the emergence of new technologies in the medical field, death itself had changed. It should be borne in mind that before 1968 an individual was considered to have died when his heart had ceased to beat. Then, the Ad Hoc Committee of the Harvard Medical School decided otherwise by identifying death upon irreversible cessation of all functions of the brain (brain death). Although this new definition of death does not resolve questions of ontological, moral and scientific nature, it has been accepted by the majority of national courts because of its practical usefulness and above all because it favours transplant (vital organ) medicine. This new definition thus seems to be based on pragmatic considerations rather than empirical evidence. Thus, when the issue is deepened, it is discovered that it is not a proper definition of human death. Following the intellectual path of the famous Italian neurologist Carlo Alberto Defanti, this work involves analysing the main “thresholds” (brain death, heart death, cortical death) to see whether there is an adequate definition of human death. The limitations and weaknesses of each definition have led to the search for an alternative perspective that could solve moral problems in particular, with a view to making public opinion more aware and accountable to death.