Smoking is per se a major risk factor in cardio-vascular diseases. It causes atherosclerosis and blockage particularly in the aorta and the leg arteries. The components of tobacco smoke damage the endothelium, increase arterial contractility, and accelerate the formation of plaque therein. The mechanisms of the effect of smoking on the genesis of atherothrombotic diseases have been studied in inter alios identical twins where the one smokes and the other does not. Smoking activates the sympathetic nerves and affects their regulation. Tobacco smokers show signs of activated thrombocyte function and increased sensitivity to vasoconstriction, which provokes a counter-reaction in the arterial walls. The observations emphasize the importance of vaso-active agents for the development and complications of atherosclerosis.