Apoptosis is a term first used in 1972 by Kerr et al. to describe a tissue pathology known as “shrinking necrosis” . Today, the term refers to a mechanism by which cells die in an orderly manner through a genetically governed event (programmed cell death) or via the triggering of a series of parallel, cross-talking pathways that induce orderly cell death. The hallmarks of apoptosis are DNA condensation and fragmentation, loss of cell volume, membrane blebbing, externalization of phosphatidylserine, protease activation, and the loss of mitochondria membrane potential; one or more of these hallmarks may be absent depending on the trigger and pathways adopted during apoptosis [2 and references therein]. As outlined in Figure 5.1, two central pathways lead to apoptosis: (1) positive induction by ligand binding to a plasma membrane death receptor, and (2) negative induction by loss of a suppressor activity involving the mitochondria [2,3]. Each pathway feeds into the activation of a pivotal group of thiol aspartatespecific proteases, i.e., caspases. Caspases are activated by a wide range of stimuli from death receptors, Granzyme B/perforin, loss of survival signals (hormones, cytokines, and serum withdrawal), redox stress, and ultraviolet light and irradiation, to the release of cytochrome c (cyt c) and other death promoting factors (such as AIF (apoptosis inducing factor) and Smac/DIABLO) from the mitochondria into the cytosol, all of which serve as triggers to activate caspases [4 and references therein]. In the classic death receptor model of Fas receptor (FasR(CD95/Apo1)) activation, the Fas ligand (FasL(CD95/Apo1L)) exists as a homotrimeric membrane molecule, with each FasL(CD95/Apo1L) trimer binding three FasR(CD95/Apo1) molecules on the surface of the target cell . This results in the death inducing signaling complex (DISC) that is a complex of Fas (trimer), Fas-associated death domain (FADD), and procaspase-8. Upon recruitment by FADD, procaspase-8 oligomerization drives its self-activation through autoprocessing, and active caspase-8 then activates downstream caspases, committing the cell to apoptosis. The mitochondria play an active role in apoptosis, which is regulated by a group of proteins known as the Bcl-2 family of proteins (antiapoptotic, Bcl-2, Bcl-XL; and proapoptotic, Bad, Bax, Bid, Bak) . Whereas antiapoptotic members of the Bcl-2 family protect mitochondrial integrity by inhibiting membrane depolarization/permeabilization and translocation of death amplifying protein, the proapoptotic counterparts neutralize these effects by dislodging antiapoptotic members from the mitochondria and forming oligomers that function as channels for the release of transmembrane proteins. The cytosolic cyt c triggers the recruitment of the protein Apaf-1 (apoptotic protease activating factor-1), procaspase-9, and dATP, to bring about the assembly of the apoptosome . Apoptosome formation triggers activation of caspase-9, which accelerates apoptosis by activating other caspases.