Reversible acetylation of histones is a well-known mechanism of epigenetic regulation of gene expression. More recently, studies have demonstrated that acetylation/deacetylation in several proteins regulate multiple aspects of cellular activity, especially those associated with energetic metabolism. Platelets are key participants in haemostasis and cardiovascular diseases. Although metabolic changes such as diabetes or lipidemia are well recognized risk factors for cardiovascular diseases, there is very little information about the relationship between metabolism and platelet reactivity. Recent studies have reported that different aspects of platelet function such as adhesion, aggregation, or granule release could also be regulated by acetylation of proteins. These cycles of acetylation/deacetylation are regulated by the contrasting action of acetyltransferases and deacetylases, which have been described by the presence of p300 and HDAC6, and sirtuins, respectively, in platelets. Remarkably, deacetylases, especially sirtuins, have been the subjects of intensive pharmaceutical research due to their implication in several physiological and pathological processes in organisms. The discovery of acetylation mechanisms in platelets opens new possibilities for the treatment and prevention of cardiovascular diseases through the regulation of acetylases/deacetylases in platelets. Therefore, the aim of this review is to present some recent reports concerning the role of acetylation of proteins in the control of platelet function, and the new possibilities of regulation of platelet function that this represent.