Senescence, or aging, of cells, tissues, or an entire organism is characterized by a gradual functional decline because of physiologic, histologic, and biochemical changes with the passage of time. Scientists believe senescence originates primarily from alterations in the genome. The accumulation of mutations in stem cells and how these mutations relate to human aging and tissue homeostasis is a complex topic and has only recently begun to be elucidated. Since stem cells are involved in homeostasis, regeneration, and repair of tissues, the decreased functionality of old age implies that impaired stem cell function may be directly responsible. Accordingly, a greater understanding of stem cell mutagenesis holds promise in oncologic and regenerative medicine.