Sirtuins are NAD+ dependent enzymes that have a predominant role in neurodegenerative disorders and also regulate the inflammatory process, protein aggregation, etc. The relation between Sirtuins with that of the nervous system and neurodegeneration are widely studied consequently. Sirtuins have a strong role in metabolic syndrome in mitochondria also. The activities of Sirtuins can be altered by using small molecules that would be developed into drugs and it is proven that manipulation of SIRT1 activity influences neurodegenerative disease models. They are especially thrilling since using small molecules, which would be developed into a drug, it is feasible to alter the activities of sirtuins. Different functions of Sirtuins are depended upon their subcellular localization. In this review paper, we are discussing different Sirtuins, differential expression of sirtuins, and expression of sirtuin in the brain and briefly about sirtuin3 (SIRT3).