One of the most obvious characteristics of the aging process is the progressive decline in the regenerative potential of tissues. Adult somatic stem cells are critical for rejuvenating tissues and persist throughout the lifespan of organisms. However, stem cell function declines during the aging process in tissues such as the brain, blood, skin, intestinal epithelium, bone, and skeletal muscle. This demise may contribute to tissue degeneration, organismal aging, and age-related diseases. A series of organismal models have emerged as valuable systems to study stem cell aging in vivo. Here, we review the age-associated changes of stem cells and the different organismal models used to define stem cell aging.