Normal cells can respond to DNA damage, telomere dysfunction, and other potentially oncogenic events by entering an essentially irreversible state of arrested growth and altered function termed cellular senescence. Multiple lines of evidence indicate that the senescence response is an important mechanism for preventing the development of cancer among mammals. However, there is also evidence that cellular senescence may be an example of evolutionary antagonistic pleiotropy. That is, whereas the senescence response curtails malignant tumorigenesis early in life, the accumulation of dysfunctional senescent cells later in life may promote aging phenotypes and certain age-related pathologies, including late life cancers. One can imagine two possible strategies for ameliorating the deleterious effects of senescent cells. The first is to eliminate them, for example by apoptosis. This strategy depends on the ability to identify senescence-specific antigens or promoters in order to selectively target toxins or express pro-apoptotic proteins in senescent cells. The second strategy is to reverse the senescent phenotype, ideally without reversing the senescence growth arrest. This strategy requires a better understanding of the apparently irreversible nature of the senescent phenotype. We and others have recently gained insights into this phenomenon. Some senescent human fibroblasts apparently acquire a heterochromatin structure owing the activity of the RB tumor suppressor. This chromatin persists, even if RB or its upstream regulator p16, is subsequently inactivated. Other human fibroblasts, however, do not acquire this irreversible chromatin. We were recently successful in reversing the senescence growth arrest of such cells.