One of the hallmarks of lung cancer is the deregulation of apoptotic or programmed cell death mechanisms usually found in normal cells that allow for corrupted cells to undergo cellular suicide. This includes mechanisms that attenuate proapoptotic pathways and/or amplify antiapoptotic pathways. Increasing evidence suggests that lung cancer cells use multiple and perhaps redundant pathways to maintain survival. Increasing knowledge of these pathways offers a better understanding of the biology of lung cancer as well as novel therapeutic strategies that can enhance lung cancer cell death. This review discusses the apoptotic machinery and signal transduction pathways that regulate apoptosis, methods of identifying the presence of activated survival signaling pathways in human lung cancers, and the clinical significance and relevance for therapy for patients with lung cancer.