Proliferative expansion of lymphoid cells is required for effective immune responses against invading microorganisms, but after the infection is controlled, the expanded effector cells must be eliminated to prevent non-adaptive accumulation of cells. Higher vertebrates have developed extensive networks of signal transduction pathways to ensure controlled activation and expansion of cells during immune responses and apoptotic deletion of lymphoid cells that are no longer needed at the end of immune responses. Extracellular signals received by cell surface receptors that trigger intracellular signaling cascades are essential elements that control both processes. These signal transduction pathways converge to regulate cell fate at both transcriptional and post-transcriptional levels. Here we review the role of pathways, especially those triggered by TNF receptor-related molecules, that determine the fate of T cells during development and activation. In addition, we introduce the possibility that these same pathways may be abnormally programmed and so lead to immune cell accumulation during inflammatory diseases such as asthma.