Replicative senescence is a fundamental feature of most, if not all, somatic higher eukaryotic cells. The phenomenon has been studied for more than three decades, during which time the genetics and cell biology of senescent cells were characterized. In recent years, progress has been made on understanding the molecular basis for replicative senescence. At present, we now have a good, albeit still incomplete, understanding of some of the immediate causes for the growth arrest of senescent cells. The challenges for the future will be to understand the molecular bases for the prime causes of senescent phenotype, including the growth arrest and the altered differentiation.