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 human 45 kDa DNA fragmentation factor (DFF45) was identified recently that was cleaved by caspase-3 during apoptosis. Mouse homologue of human DFF45 was identified as a DNase inhibitor designated ICAD. DFF45/ICAD have short forms that were termed DFF35 and ICADs, respectively. Upon cleavage of DFF45/ICAD, the caspase activated deoxyribonuclease (DFF40/CAD) is released and activated and eventually causes the degradation of DNA in the nuclei. Therefore, the cleavage of DFF45/ICAD, which causes DFF40/CAD activation and DNA degradation, is the hallmark of apoptotic cell death.