Tobacco smoking is the most important preventable cause of cardiovascular disease. In this paper we review current epidemiological and pathophysiological evidence linking smoking with cardiovascular and metabolic diseases. Among the effects of smoking there is the alteration of lipid metabolism through the increase in lipolysis, insulin resistance and tissue lipotoxicity. Smoking is both prothrombotic and atherogenic. As an effect, the risk of acute myocardial infarction, sudden cardiac death, stroke, aortic aneurysm and peripheral vascular disease is increased. Even very low doses of exposure increase the risk of cardiovascular disease (CVD) and metabolic alterations. On the other hand, smoking cessation restores, at least in part, lipid metabolism and the benefits can be observed already after a short period of abstinence from smoking, although it occurs several years before the risks approach those of the never-smoker.