Cells of multicellular organisms require extracellular signals to survive. Numerous studies have implicated a variety of intracellular signaling pathways, including PI-3 kinase/Akt, Ras/mitogen-activated protein kinase, and Jak/signal transducers and activators of transcription, as effectors of these extracellular trophic factors. Binding of growth factors to their respective receptors results in the activation of individual and combined pathways resulting in pleiotropic effects on cellular biochemistry. Over the past decade, investigation of these pathways has provided insight into the mechanism of cell survival and apoptosis itself. The results of these studies are providing new clues for therapeutic intervention in human disease. In this review, we focus on advances in our current understanding of the receptor signaling pathways that regulate apoptosis. Implications for the pharmacological manipulation of apoptosis in the treatment of cancer are also discussed.