Autophagy has become a biological paradigm of how eukaryotic cells, especially those that are long lived, maintain their vitality, control the quality of cytoplasmic organelles, and stay alive or die when growth factors are withdrawn and there is an energy or nutrient crisis. The role of autophagy has been extended to innate and adaptive immunity functions, which surpassed all initial expectations in terms of how immunity and autophagy are interconnected. Of particular interest at the moment is the growing appreciation of the similarity between how mitochondria and intracellular pathogens are handled by autophagy in its function of sanitizing the cytoplasm. An emerging framework from this may link the roots of cell defense against infection with cell longevity and programmed cell death.