Our bodies are societies where survival of the whole is achieved at the expense of individuals. From the moment we are conceived, proliferation and differentiation establish an astounding diversity of cellular forms and functions, from light-sensing photoreceptors to enucleated red blood cells [1]. Cell survival and death first sculpt and then maintain animal organs and tissues [2], [3], [4], [5], [6], [7]. For instance, cell death eliminates a thin layer of skin between our digits during embryonic development, preventing us from being born with webbed hands and feet [8], [9], [10]. Throughout our lives, death of older cells and birth of new ones maintain homeostasis in many tissues, including the gut and the skin [11].

Crucially, cell death allows for competition to select the most fit units to build a tissue. For example, competition for trophic factors and apoptosis shape the nervous system during development [12], [13]. Mechanical competition for space can also lead to death of loser cells [14], [15]. Central to all of these processes is a cellular choice: whether to live or die. In this review, we critically analyze the concept that cell death signaling is irreversible, describe the biochemical mechanisms and the implications for organism development and homeostasis. To begin, we describe how apoptotic signaling is set in action and how cellular suicide is executed.