Originally discovered as a transcriptional silencing protein, SIR2 was later linked to yeast replicative aging and the rest was history. Sir2p is now known to be a member of a class of protein deacetylases with a unique enzymatic activity coupling the deacetylation event to NAD(+) hydrolysis. While still incompletely understood, the mechanism by which Sir2p modulates yeast aging is linked to inhibition of rDNA recombination. Here we describe phenotypes associated with yeast Sirtuins and assays used to monitor Sirtuin function in yeast, including the replicative aging assay.