Saccharomyces cerevisiae is a commonly used aging model. Aging in yeast is assayed primarily by measuring replicative lifespan (RLS) or chronological lifespan (CLS). Several longevity factors have been identified through RLS and CLS studies, including Sirtuins (Sir2 protein family members). Sirtuins are well-known aging factors and a class of NAD dependent protein deacetylases that are evolutionarily conserved from prokaryotes to higher eukaryotes. Sirtuins exhibit multiple intracellular functions, including stress response, gene transcription, cellular metabolism, and longevity. The Sir2 protein is the founding sirtuin family member that functions in transcriptional silencing of heterochromatin domains and as a pro longevity factor for replicative lifespan. Deleting SIR2 shortens replicative lifespan, while increased gene dosage causes extension. Furthermore, Sir2 homologs in higher eukaryotes have been implicated in mediating age related diseases as well. In this review, we summarize the role of Sir2 and its yeast homologs, Hst1 through Hst4, in replicative aging and chronological aging.