Human cells in culture have been used for over 30 years as models to examine the biology of aging. Some studies suggest that cellular aging is a genetically dominant characteristic; other studies suggest that aging is characterized by a general dysregulation of processes and pathways. A question of major interest is to what extent replicative senescence in culture provides insights about senescence in the organism. Overall, the findings suggest that there may be multiple cellular pathways to acquiring the senescent phenotype, some more relevant to organismic aging than others. Nevertheless, by studying processes in cell cultures that are known to fail in aging, we can learn the cellular and molecular bases of these failures.