Since healthy aging remains one of the ideals of modern society, both, the identification of the underlying molecular mechanisms and interventions regarding the aging process are of considerable interest. Among the mechanisms currently being considered, the sirtuin family of histone deacetylases have been implicated to play a crucial role during the aging process both due to their requirement of NAD(+) as a cofactor for enzymatic activity, which determines a crucial link between sirtuins and the energy dependent regulation of gene transcription and their versatile target substrates mainly consisting of key regulators of metabolic, stress and cell cycle control. This chapter summarizes current evidences linking sirtuins to aging and outlines their potential as promising therapeutic targets for the treatment of age-related diseases.