Autophagy is an evolutionarily conserved process in eukaryotes by which cytoplasmic components including macromolecules and organelles are degraded by the lysosome/vacuole. Autophagy is implicated in a number of physiological processes important for human health and disease. Although primarily cytoprotective, autophagy can also contribute to cell death; it is thus important to understand what distinguishes the life or death decision in autophagic cells. Despite the fact that the execution of autophagy includes a unique set of cytoplasmic events, nuclear events, in particular transcriptional programs, have emerged as an important regulator of this process. In addition, a critical linkage was recently unveiled between specific histone posttranslational modifications and the transcriptional regulation of autophagy-related genes, which initiates a regulatory feedback loop, and serves as a key determinant of survival versus death responses upon autophagy induction.