The understanding of the apoptotic program has grown exponentially over the past decade. Numerous human diseases have been directly linked to genetic defects in the apoptotic pathways, including cancer, neurodegenerative disorders, and autoimmune diseases. Caspases initiate and amplify various death signals, allowing for selective and ordered cellular demolition. The fine balance between pro- and antiapoptotic Bcl-2 family members regulates the cell fate in response to many (but not all) stress or signaling pathways. Recent discoveries highlight the complex integration of signals from various organelles that determine cell fate and the multiple functions of central players in the apoptotic process. It is likely that the knowledge obtained in a relatively time will translate into better diagnostics and therapies to enhance or retard cell death in the appropriate clinical circumstances.