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T cells are crucial for clearance of pathogens and providing protection against re-infection. Functional T cells should be capable of recognizing foreign proteins while being tolerant to self-proteins so as to prevent autoimmunity. Apoptosis regulates thymic selection to ensure the survival and maturation of tolerant, functional T cells. In the periphery, apoptosis regulates the survival of the fittest T cells to help fight infection and become memory T cells, which is the goal of most vaccine strategies. In this dissertation, we aimed to study the role of anti-apoptotic proteins of the Bcl-2 family in thymic selection and survival of effector and memory CD4 T+ cells after lymphocytic choriomeningitis virus (LCMV) infection of mice. As the pro-apoptotic Bcl-2 family member, Bim is critical to regulate both thymic selection and peripheral survival, we focused on the anti-apoptotic proteins that allow some T cells to avoid Bim-mediated death. In Chapter II, we report that Bcl-2 promotes the survival of thymic precursors of TCRaß+CD8aa+ IEL by antagonizing Bim. Bcl-2 was highly expressed in PD-1+ CD122+ thymic IEL precursors that experienced strong agonist signals. Further, we found distinct subsets within PD-1+CD122+ IELp based on their expression of Runx3 and a4ß7. Notably, IELp that co-expressed Runx3 and a4ß7 displayed the highest Bcl-2 dependence. Further, mice with loss of Bcl-2 at the early DP stage were virtually devoid of TCRaß+CD8aa+ IEL. Therefore, Bcl-2 was critical for both promoting survival of thymic IELp and maintaining survival of gut TCRaß+CD8aa+ IEL. In Chapter III, we found that specific anti-apoptotic Bcl-2 family members controlled the survival of CD4+ T cell subsets during distinct phases of mouse acute LCMV infection. Prior studies and our single-cell transcriptomics of CD4+ LCMV-specific effectors helped distinguish T helper 1, germinal center T follicular helper (GC-Tfh), T central memory precursors (Tcmp) and CD4+ cytotoxic (CD4 CTL) T cell subsets. Temporal deletion of the anti-apoptotic proteins, Bcl-2 and A1 revealed that during the effector phase, A1 was critical for the survival of all CD4+ effector subsets. While Bcl-2 in combination with A1 was important for Tfh and Tcmp effector survival, Th1 effector survival was independent of Bcl-2. During contraction, Bcl-2 was critical in Th1 and Tcmp subsets to antagonize Bim. Furthermore, Tcmp died significantly less compared to Th1, likely due to their high expression of Bcl-2. However, A1 and Bcl-2 redundantly controlled the survival of GC Tfh and CD4 CTL. Neutralization experiments during contraction revealed that IL-7 drove the survival of all CD4 effector subsets, except CD4 CTL. Finally, we showed that long-term memory CD4+ T cell survival critically depended on Bcl-2. Chapter IV summarizes our novel findings, proposes future directions and potential for translation impact. Finally, one literature review on the role of cell death in T cell homeostasis, with emphasis on Bcl-2 family members, is included in the Appendix. Overall, our data demonstrate temporal and subset-specific roles of the anti-apoptotic Bcl-2 family of proteins in regulating the thymic development of intestinal intraepithelial lymphocytes and effector and memory CD4+ T cell survival during viral infections.