For most of this century, tissue death and the cells involved were, with rare exceptions, made synonymous with necrosis. Serious challenge to this overarching dogma began with the presentation of strong evidence for a second form of cell death named apoptosis, characterized by a variety of morphological and biochemical differences from necrosis (1,2). Wide acceptance of this novel concept of nonnecrotic cell death was temporarily delayed by a vigorous dissent from a large number of biochemically oriented scientists who insisted that their term of “programmed cell death” was more suitable and that apoptosis was a flawed concept (3). Although both terms (apoptosis and programmed cell death) currently remain in use by investigators, and lively debate continues as to whether they are the same or different conditions, increasingly wide acceptance of the concept of apoptosis has now established it as importantly different from necrosis, in large measure because it explains many examples of unequivocal cell death that simply cannot be legitimately diagnosed as necrosis. This certainly is true for fetal and postnatal morphogenesis of a variety of tissues and organs, including the human heart (4,5). Based on current knowledge, it is unwise to use apoptosis and programmed cell death as interchangeable terms, but there is clearly substantial overlap between them. Most of the original morphological descriptions of apoptosis remain valid and include the following. Apoptotic cells either shrink or do not change size, whereas necrotic cells typically swell. The plasmalemma of apoptotic cells remains intact, but this external cell membrane of necrotic cells promptly ruptures. Most organelles (mitochondria, sarcoplasmic membrane, and so forth) of apoptotic cells remain morphologically preserved, whereas these same structures soon rupture or disintegrate in necrosis. The nucleus of apoptotic cells typically partitions its chromatin marginally and then the nucleus is cleaved into separate membrane-bound particles (apoptotic bodies), while the necrotic nucleus randomly clumps its chromatin as the nucleus itself disintegrates. Histologically, necrosis is characterized by all the consequences of cellular disintegration including tissue acidosis and the rapid chemotactic attraction of lymphocytes and neutrophils. By contrast, apoptotic cells quickly exteriorize molecules of phosphatidylserine from their normal internal location, thereby signalling macrophages (and even like cells such as neighboring myocytes) to engulf them, leaving the apoptotic focus of cell death conspicuously devoid of inflammation. If phagocytosis fails, for whatever reason, apoptotic cells eventually disintegrate, releasing their internal contents, and then become indistinguishable from necrosis. Sites of apoptosis in the myocardium, where local capacity for phagocytosis has not been exceeded, resemble a well-tended garden (Figure 1), whereas the morphological chaos of necrosis morpholog