Apoptosis is related to many diseases and induced by a family of cell death receptors and their ligands. Cell death signals are transduced by death domain containing adapter molecules and members of the caspase family of proteases. These death signals finally cause the degradation of chromosomal DNA by activated DNase. A mouse DNase that causes DNA fragmentation was identified recently and designated CAD (for caspase activated deoxyribonuclease). The human homologue of mouse CAD was more recently identified by three groups independently and termed CPAN, DFF40, and human CAD, respectively. DFF45/ICAD is the inhibitory protein of DFF40/CAD and forms complex with DFF40/CAD. Upon cleavage of DFF45/ICAD by activated caspase, DFF40/CAD is released and activated and eventually causes the degradation of DNA in the nuclei. Activation of DFF40/CAD, which causes DNA degradation, is the hallmark of apoptotic cell death.