Apoptosis, is a form of programmed cell death essential for the development and maintenance of multicellular organisms. DNA degradation is one of the hallmarks of apoptosis. The central component of the apoptotic machinery is a proteolytic system involving caspases and non-caspases proteases. CAD, a caspase-activated DNase, is the endonuclease responsible for DNA degradation during caspase-dependent apoptosis. The relationship between non-caspase proteases and endonucleases is less clear and up to now only the activation of GAAD by granzyme A and L-DNase II by serine proteases has been established. DNA degradation in apoptosis has been considered, either, as essential for this form of cell death, or completely usefulness. Recent data indicate that an improper digestion of DNA can block apoptosis, showing that this terminal event is important in the control of apoptosis.