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Mammalian germline cells, embryonic stem cells, and adult stem cells hold the potential for defining, constructing, and maintaining a unique individual through the respective processes of gametogenesis, embryogenesis, and tissue repair over the span of a lifetime. Autophagy carries out critical functions in these cells using a variety of mechanisms. Of particular importance to the integrity of germline and stem cells are (1) the removal of damaged and/or excess mitochondria, thereby reducing the potential for generating reactive oxygen species that can damage genomic content; (2) the removal and recycling of cellular structures to facilitate the extensive remodeling that occurs during the initial establishment and subsequent differentiation of these cell populations; and (3) the supply of substrates and energy sources when needed under stress and in the environment of the “hypoxic niche” that these cells often occupy.