Human death is a unitary phenomenon that physicians can determine in two ways: (1) showing the irreversible cessation of all brain clinical functions; or (2) showing the permanent cessation of circulatory and respiratory functions. Over the last 40 years the determination of human death using neurological tests ("brain death") has become an accepted practice throughout the world but has remained controversial within academic circles. Brain death has a rigorous biophilosophical basis by defining death as the irreversible loss of the critical functions of the organism as a whole. The criterion best fulfilling this definition is the irreversible cessation of all clinical functions of the brain. Competing definitions, such as those within the higher brain, brain stem, and circulation formulations, all have deficiencies in theory or practice. Among physicians, the area of greatest controversy in death determination now is the use of circulatory-respiratory tests, particularly as applied to organ donation after circulatory death. Circulatory-respiratory tests are valid only because they produce destruction of the whole brain, the criterion of death. Clarifying the distinction between the permanent and irreversible cessation of circulatory and respiratory functions is essential to understanding the use of these tests, and explains why death determination in organ donation after circulatory death does not violate the dead donor rule.