Apoptosis and autophagy are two key cellular processes involved in programmed cell death. While apoptosis is the first genetically programmed death process identified, autophagy, a process that involves the degradation of cellular components, has been shown to interact with apoptosis in complex ways. In some cases, autophagy can suppress apoptosis and promote cell survival, while in others, it can lead to cell death, either in collaboration with apoptosis or as a backup mechanism when apoptosis is defective. The molecular regulators of both pathways are interconnected, and they share several genes critical for their execution. The cross-talk between apoptosis and autophagy is complex and sometimes contradictory, but it is crucial for determining the fate of the cell. This cross-talk is also key in the outcome of death-related pathologies such as cancer. Autophagy, which has long been known to provide a survival advantage to cells under stress, has also been linked to the actual death process. Thus, apoptosis is not the sole means by which a cell can undergo a genetically programmed self-elimination. Cell death can occur through several mechanisms, and the phenotypic changes that accompany cell death can vary depending on the stimulus and cell setting. In any given death scenario, the cell decides which pathway to use, depending on the nature of the stimulus and the specifics of the cell environment. Furthermore, apoptosis and autophagy are not mutually exclusive pathways. They have been shown to act in synergy and also to counter each other. They share many of the same molecular regulators. In a clinical setting, one cannot predict the outcome of inhibition or activation of one death program without considering the effect on the other. The review focuses on the cross-talk between the autophagic and apoptotic pathways, with an analysis of how this may affect the clinical applications of death suppression/activation to cancer. The process of necrosis, the third means by which the cell can undergo a genetically programmed self-elimination, will not be discussed in detail. Although not intended to provide an exhaustive summary of the recent literature, the discussion will include salient experimental results as examples of the different facets of the apoptosis/autophagy interplay. The review discusses three types of interplay between apoptosis and autophagy: partner, antagonist, and enabler. In the partner relationship, both apoptosis and autophagy cooperate to lead to cell death. In the antagonist relationship, autophagy acts to attenuate apoptosis by creating a cellular environment that favors survival. In the enabler relationship, autophagy assists the apoptotic program without leading to death itself. The review also discusses the molecular cross-talk between apoptosis and autophagy, highlighting the shared genes and pathways that regulate both processes. The review concludes that the cross-talk between apoptosis and autophagy is complex and multifaceted, and a full understanding of this relationship is critical for the assessment of anticancer strategies.Apoptosis and autophagy are two key cellular processes involved in programmed cell death. While apoptosis is the first genetically programmed death process identified, autophagy, a process that involves the degradation of cellular components, has been shown to interact with apoptosis in complex ways. In some cases, autophagy can suppress apoptosis and promote cell survival, while in others, it can lead to cell death, either in collaboration with apoptosis or as a backup mechanism when apoptosis is defective. The molecular regulators of both pathways are interconnected, and they share several genes critical for their execution. The cross-talk between apoptosis and autophagy is complex and sometimes contradictory, but it is crucial for determining the fate of the cell. This cross-talk is also key in the outcome of death-related pathologies such as cancer. Autophagy, which has long been known to provide a survival advantage to cells under stress, has also been linked to the actual death process. Thus, apoptosis is not the sole means by which a cell can undergo a genetically programmed self-elimination. Cell death can occur through several mechanisms, and the phenotypic changes that accompany cell death can vary depending on the stimulus and cell setting. In any given death scenario, the cell decides which pathway to use, depending on the nature of the stimulus and the specifics of the cell environment. Furthermore, apoptosis and autophagy are not mutually exclusive pathways. They have been shown to act in synergy and also to counter each other. They share many of the same molecular regulators. In a clinical setting, one cannot predict the outcome of inhibition or activation of one death program without considering the effect on the other. The review focuses on the cross-talk between the autophagic and apoptotic pathways, with an analysis of how this may affect the clinical applications of death suppression/activation to cancer. The process of necrosis, the third means by which the cell can undergo a genetically programmed self-elimination, will not be discussed in detail. Although not intended to provide an exhaustive summary of the recent literature, the discussion will include salient experimental results as examples of the different facets of the apoptosis/autophagy interplay. The review discusses three types of interplay between apoptosis and autophagy: partner, antagonist, and enabler. In the partner relationship, both apoptosis and autophagy cooperate to lead to cell death. In the antagonist relationship, autophagy acts to attenuate apoptosis by creating a cellular environment that favors survival. In the enabler relationship, autophagy assists the apoptotic program without leading to death itself. The review also discusses the molecular cross-talk between apoptosis and autophagy, highlighting the shared genes and pathways that regulate both processes. The review concludes that the cross-talk between apoptosis and autophagy is complex and multifaceted, and a full understanding of this relationship is critical for the assessment of anticancer strategies.