Silent information regulator 1 (SIRT1) is a type of histone deacetylase whose activity is dependent on nicotinamide adenine dinucleotide. SIRT1 plays a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of SIRT1 was reported for neurological diseases. The focus of this review is to summarize the protective effects of SIRT1 in cerebral ischemia. First, the posttranslational modifications of SIRT1 are illustrated; then, we discuss the roles of SIRT1 in cerebral immune homeostasis. Next, we introduce the deacetylase activity of SIRT1 in cerebral ischemia and provide some examples of relevant studies. In addition, we discuss several activated mediators of SIRT1, such as resveratrol, caloric restriction, ischemic preconditioning, and other proteins and compounds. Finally, we highlight a few SIRT1-related signaling pathways, such as the peroxisome proliferator-activated receptor ? coactivator 1?, nuclear transcription factor ?B, uncoupling protein 2, and forkhead box O pathways. Taken together, the information compiled in this article will serve as a comprehensive reference for the actions of SIRT1 in the nervous system and will help in the design of future experimental research and promote SIRT1 as a new therapeutic target.