Caspases are the executioners of apoptosis. These cysteine protease family consists of more than 10 related members characterized by almost absolute specificity for aspartic acid in the P1 position. Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide together with one large and one small subunit . Activation of caspases during apoptosis results in the cleavage of critical cellular substrates so precipitating the dramatic morphological changes of apoptosis. Apoptosis induced by CD95 (Fas/APO-1) and tumor necrosis factor activates caspase-8 (MACH/FLICE/Mch5) so providing a direct link between cell death receptors and the caspases, caspase-8 being at the apex of the apoptotic cascade . Caspase-8 is a 55 kDa protein binding the death effector domain of FADD . A total of eight different iso forms of FLICE have been described, only two of them being predominantly expressed . The CASP8 gene contains at least 11 exons spanning approximately 30 Kb on human chromosome band 2q33–34 . The protein encoded shows a complex tertiary structure . Apart from being activated by CD95 cleavage of caspase-8 by granzymeB during T-lymphocyte induced apoptosis has been shown. Further digomerization at the membrane turned out to be sufficient for caspase-8 autoactivation. The apoptosis induction by caspase-8 is then amplified through the mitochondrial release of cytochrome . FLIP was shown to be a regulatory protein of lymphocyte proliferation and death and germinal center B cell apoptosis, its expression inhibits T-cell activation. On the other hand FLIP(L), the long form of the protein, activates caspase-8 by forming heterodimeric structures . Caspase-8 plays an important role in all physiological disorders where apoptosis is involoved primarily in the development (and treatment) of tumors and cardiac diseases .