We suggest that the commonly observed trade-offs between early- and late-life reproduction may be mediated by genetic variation in germline stem cell maintenance. Stem cell biology provides a natural framework and experimental methods for understanding the mechanistic basis of life-history evolution. At the same time, natural variation in life-history strategies can serve as a powerful tool for identifying the genes and molecular pathways involved in the maintenance of stem cells in aging adults. We illustrate the connections between life-history and stem cells with examples drawn primarily from Drosophila melanogaster and Caenorhabditis elegans, and suggest a number of testable hypotheses and avenues for future investigation that can be addressed with existing models and tools.