Atherosclerotic cardiovascular disease is the dominant health problem in the western world. Major clinical manifestations of cardiovascular disease include myocardial infarction, coronary artery disease, stroke, peripheral artery disease and congestive heart failure. In most cases, these clinical conditions result from atherosclerosis, a progressive disease of the arterial wall, characterized by focal thickening and luminal obstruction. The old view, not more than 10 to 15 years ago, saw atherosclerosis as a simple ‘plumbing problem’ due to a gradual build-up of a plaque containing cholesterol and fatty material on the surface of the passive artery walls. Currently, new view recognizes atherosclerosis as a chronic inflammatory disease, involving many cell interactions at the level of the active vascular wall (1). The cellular and molecular mechanisms involved in atherosclerosis and its acute complications are being defined (2), but much is still unknown. Growing evidence indicates a critical role for telomere dysfunction as key causal events in the biological process of atherosclerosis and its complications. Telomeres are special DNA regions located at the ends of eukaryotic chromosomes that prevent chromosomal fusions, offering genomic integrity and stability (3). The telomeric DNA is composed of noncoding double-stranded repeats of G-rich tandem DNA sequences (TTAGGG in humans), that are extended several thousand base pairs (10 to 15 kb in humans) and end in a 150 to 200 nucleotide 3’single-stranded overhang (G-strand overhang). The synthesis of new telomeric DNA repeats in dividing cells requires the activity of telomerase and additional telomere associated proteins. Progressive telomere shortening during ageing is characteristic of most adult somatic cells, which exhibit low or no telomerase activity. In contrast to adult somatic cells, germ, stem and tumor cells maintain high telomerase activity, long telomeres and high proliferative potential. Cells affected by critical telomere attrition accumulate chromosomal aberrations and succumb to replicative senescence or apoptosis (4). During the last years, evidence for the presence of chromosomal instability in atherosclerosis has also been obtained from experimental and clinical investigations (5). Furthermore, an increasing body of evidence has established the critical role of the telomere in vascular cells (6). An age-dependent telomere shortening has been reported in ECs from iliac, thoracic, and coronary arteries (7,8). The loss of telomere function induces a senescent phenotype and endothelial dysfunction, that are observed in aged arteries, as well as functional alterations involved in atherogenesis, such as an increased expression of intercellular adhesion molecule-1 and diminished endothelial nitric oxide synthase activity. Interestingly, inhibition of telomere shortening suppressed both EC senescence and associated functional alterations (9) Shorter telomeres in coronary ECs from atherosclerotic coronary arteries compared with those at non-atherosclerotic specimens (9). Similarly, plaque VSMCs also show multiple markers of senescence, accelerated both in vivo and in vitro by oxidative stress-induced DNA damage, inhibition of telomerase, and marked telomere shortening (10). Available observational data show an inverse association between telomere length in human blood cells and risk of age-associated vascular diseases (3,6). A pilot study found that patients with early-onset coronary artery disease with premature myocardial infarction had a shorter mean LTL compared with healthy subjects of the same age and gender (11). The West of Scotland Primary Prevention Study also demonstrated that that the risk of developing CAD was highest in individuals with short telomeres and that this risk was substantially attenuated by treatment with pravastatin (12). However, a large prospective study of patients with stable CAD found that leukocyte telomere length is associated with mortality independently of chronological age, clinical factors, echocardiographic variables and no difference in mean telomere length between users and nonusers of statins (13). In a large cohort of 620 CHF patients compared to 183 age- and gender- matched controls (14) Telomeres were shown to be related to the severity of heart failure as they were shorter in patients with higher New York Heart Association class (14). Furthermore, there are suggestions that telomere length is associated with reduced ejection fraction in the elderly (15). A recent meta-analysis indicates that telomere length is inversely associated with risk of coronary heart disease independently of conventional vascular risk factors (16). Whether telomere testing is clinically useful predictor of risk that can help guide treatment decisions, however, will require further evaluation in large prospective studies with long follow-up Furthermore, anti-aging therapies that modulate telomere length are expected to have an impact various age-related diseases.