In healthy tissues, there is a balance between cell survival and death. This balance ensures epithelial cells survive in the right milieu, but undergo programmed cell death (apoptosis) when the environment is no longer supportive. Cells sense these changes primarily through receptors on the cell surface that bind to specific ligands present in the extracellular environment. These receptors, through signal transduction pathways, lead to promotion of cell survival or induction of cell death. One of the most important types of receptors regulating cell survival is the epidermal growth factor (EGF) receptors, while one of the most important types of receptors regulating apoptosis is the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors. EGF receptors activate survival signaling pathways including PI3K/AKT, Ras/MAPK, and JAK/STAT signaling pathways leading to cell survival. TRAIL activates apoptotic signaling pathways leading to caspase activation and mitochondrial dysfunction. The balance between these two signaling pathways determine whether a cell survives or dies. In disease states, this balance is altered. For example, epithelial-derived cancer cells often have increased expression of EGF receptors and are resistant to apoptosis. Understanding the interactions between survival and apoptotic signaling pathways mediated by EGF receptors and TRAIL death receptors will be essential to explain the role these pathways play in healthy and diseased cells.