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. The CED/ICE family of cysteine proteases plays a critical role in mediating such apoptosis. A human DNA fragmentation factor (DFF) was identified recently which is cleaved by caspase-3 during apoptosis. Mouse homologue of human DFF was identified as a DNase inhibitor designated ICAD, for inhibitor of caspase-activated DNase. Upon cleavage of DFF/ICAD, a caspase activated deoxyribonuclease (CAD) is released and activated which eventually causes the DNA fragmentation in the nuclei. Therefore, the cleavage of CAD inhibitor molecule DFF/ICAD, which causes DNase activation and DNA degradation, is the hallmark of apoptotic cell death.