Abstract: Apoptosis, or the programmed cell death, is employed by eukaryotes to eliminate damaged or unwanted cells tomaintain homeostasis. Unlike necrosis, apoptosis is an active, genetically controlled sequence of events which involve the activation, expression and regulation of multiple genes. Apoptosis reflects a strategy of cells to adapt to a changing environment rather than passive self-damage under pathological conditions. Malfunction of apoptosis, either being “too much” or “too little”, has been implicated in various diseases, including tumorigenesis. Due to the critical roles apoptosis play in maintaining tissue homeostasis, pro- and anti-apoptotic signals are carefully balanced within cells. This balance is achieved through the products of a series of apoptosis-related genes, including the anti-apoptotic IAP (inhibitor of apoptosis protein) family, the pro-apoptotic caspase protease family, the p53 tumor suppressor as well as recently characterized non-coding RNAs such as microRNAs. Through directly or indirectly interacting with each other, these factors constitute a complex signaling network whose overall function determines the progress of apoptosis and ultimately, the fate of the cell. Defining the molecular mechanisms by which each factor contributes to apoptosis will not only deepen our understanding of cell physiology and the origin of life, but also enable a more rational approach to anticancer drug design and therapy.