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Cigarette smoke is a complex mixture of about 7,000 different toxic substances, many of which are generated during the burning of the tobacco leaf, some in the gas phase and others in the particulate matter. The gas phase represents approximately 60% of the smoke from the burning of tobacco, 99% of this phase is composed of nitrogen, oxygen, carbon dioxide, carbon monoxide, hydrogen, argon, and methane. Atherosclerosis associated with smoking is not necessarily an effect of nicotine, but probably the joint action of the various constituents of cigarette smoke. ROS from the gas phase of tobacco contributes to the onset and progression of atherosclerosis. Bupropion and varenicline are used for smoking cessation despite the side effects; however, we are still far from effective treatment to assist the definitive discontinuation of the habit of smoking. This review discusses the main mechanisms associated with vascular damage from the smoking.