AbstractEmerging evidence suggests the growing importance of “nongenetic factors” in the pathogenesis of atherosclerotic vascular disease. Indeed, the inherited genome determines only part of the risk profile as genomic approaches do not take into account additional layers of biological regulation by “epi”-genetic changes. Epigenetic modifications are defined as plastic chemical changes of DNA/histone complexes which critically affect gene activity without altering the DNA sequence. These modifications include DNA methylation, histone posttranslational modifications, and non-coding RNAs and have the ability to modulate gene expression at both transcriptional and posttranscriptional level. Notably, epigenetic signals are mainly induced by environmental factors (i.e., pollution, smoking, noise) and, once acquired, may be transmitted to the offspring. The inheritance of adverse epigenetic changes may lead to premature deregulation of pathways involved in vascular damage and endothelial dysfunction. Here, we describe the emerging role of epigenetic modifications as fine-tuners of gene transcription in atherosclerosis. Specifically, the following aspects are described in detail: (1) discovery and impact of the epigenome in cardiovascular disease, (2) the epigenetic landscape in atherosclerosis; (3) inheritance of epigenetic signals and premature vascular disease; (4) epigenetic control of lipid metabolism, vascular oxidative stress, inflammation, autophagy, and apoptosis; (5) epigenetic biomarkers in patients with atherosclerosis; (6) novel therapeutic strategies to modulate epigenetic marks. Understanding the individual epigenetic profile may pave the way for new approaches to determine cardiovascular risk and to develop personalized therapies to treat atherosclerosis and its complications.