Atherosclerotic cardiovascular disease remains the leading cause of death in industrialized nations despite major advances in its diagnosis, treatment and prevention. With increasing rates of obesity, this trend will likely continue. Even though obesity serves as an independent cardiovascular disease risk factor, it also increases the incidence of other risk factors, notably diabetes, dyslipidemia, hypertension, and the prothrombotic state. Adipose tissue is an active endocrine and paracrine organ that releases a large number of cytokines and bioactive mediators that influence not only body weight homeostasis, but also inflammation, coagulation, fibrinolysis, insulin resistance, diabetes, atherosclerosis and some forms of cancer. In this review, we explore the cellular mechanisms linking obesity and atherosclerosis, highlighting the role of adipokines in endothelial dysfunction and atherogenesis, and summarize the experimental and clinical evidence on how excess body fat influences cardiovascular health.