Sirtuins (SIRTs), nicotine adenine dinucleotide (+)-dependent histone deacetylases, have emerged as critical regulators in many signalling pathways involved in a wide range of biological processes. Currently, seven mammalian SIRTs have been characterized and are found across a number of cellular compartments. There has been considerable interest in the role of SIRTs in the brain due to their role in a plethora of metabolic- and age-related diseases, including their involvement in learning and memory function in physiological and pathophysiological conditions. Although cognitive function declines over the course of healthy ageing, neurological disorders including Alzheimer's disease (AD) can be associated with progressive cognitive impairments. This review aimed to report and integrate recent advances in the understanding of the role of SIRTs in cognitive function and dysfunction in the context of AD. We have also reviewed the use of selective and/or natural SIRT activators as potential therapeutic agents and/or adjuvants for AD.