Sirtuins are a family of nicotinamide adenine dinucleotide (NAD + ) dependent deacetylases involved in multiple biological functions including metabolism, inflammation, stress resistance and aging. In mammals, there are seven members (Sirt1-Sirt7), with diversities in their subcellular localizations and enzymatic activities. Here, we review the functions of sirtuins, with a focus on their roles in normal brain physiology such as neural development regulation, body homeostasis maintenance, and memory formation. We also discuss the role of sirtuins in a variety of brain diseases including stroke, Alzheimer's, Parkinson's, and motor neuron dysfunction. Because of the emerging functions of sirtuins in brain physiology and pathology, drugs targeting sirtuins may offer potential therapeutic values for brain disorders.