Age-related diseases pose as an enormous problem on aging populations of the world. Despite the fact that many advances have been made on understanding of the neurodegeneration, there is still no cure available for the age-related brain disorders. Sirtuins are NAD-dependent protein deacetylases that were shown to have beneficial effects against age-related diseases. SIRT1 and SIRT2 have been studied mostly in terms of neurodegenerative diseases and seem to have opposite effects. According to the recent findings, activators of SIRT1 and inhibitors of SIRT2 would benefit the brain from neurodegeneration. Despite the enormous amount of research that has been conducted so far, there is still no cure or treatment for almost all of the neurodegenerative disorders. In addition, the mechanisms underlying brain aging and also the link between aging and neurodegeneration are not understood. This review focuses on the role of sirtuins as possible drug targets for neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's Diseases.