Over the years, our work has highlighted the critical role of an altered redox metabolism on cell survival and death signaling in cancer cells (Clement, M-V.and Pervaiz, S.2007).Using a variety of model systems such as drug-induced apoptosis, receptor mediated death signaling, and oncogene-induced cell survival, we demonstrated that the intracellular ratio between the two main reactive oxygen species (ROS), superoxide and hydrogen peroxide, determines cancer cell response to death signals;a tilt in favor of superoxide promotes cell survival whereas an increase in hydrogen peroxide favors death execution via activation of the death promoting protein Bax (Clement, M-V.et al.2003;Ahmad,K.A.et al.2004;Hirpara, J.L.et al., 2001).Of note, more recent work from our group has focused on identifying the molecular mechanisms underlying the differential effect of the two reactive oxygen intermediates on cell fate signaling.To that end, we have highlighted a novel biological activity of Bcl-2 by providing experimental evidence linking Bcl-2-induced increase in mitochondrial superoxide levels to the anti-apoptotic activity of Bcl-2.Our follow up work on identifying the molecular mechanisms underlying this novel biology of Bcl-2 has unraveled two novel Bcl-2 interacting partners (Va subunit of mitochondrial complex Ⅳ and the small GTPase Rac 1), and linked these interactions to not only the anti-apoptotic activity of Bcl-2 but also to the ability of Bcl-2 to regulate mitochondrial metabolism and cellular redox status (Chen, Z.X.and Pervaiz, S.2007;2010;Velaithan, R.et al.2011).Interestingly,blocking the interaction of Bcl-2 with Rac1 restored death sensitivity in Bcl-2 overexpressing cancer cells, thereby pointing to a new paradigm in the context of carcinogenesis with potential therapeutic implications.