Smoking (tobacco addiction) is the most significant of the modifiable cardiovascular risk factors. Mistakenly described as a "habit" or "behavioral choice," the onset of tobacco addiction quickly follows the acquisition of an ability to inhale cigarette smoke and is reflected in a transformation of neurophysiologic function and nicotine-receptor density. Thereafter, comfort and a degree of neurophysiologic "equanimity" require the regular administration of nicotine. Smokers inhale thousands of other chemicals, many of which play critical roles in the initiation and accentuation of atherosclerosis by influencing vasomotor activity, vascular dysfunction, oxidation of lipids, atheroma development, and thrombosis. Smoking cessation is a priority in the management of any patient with cardiovascular disease. The benefits of cessation accrue rapidly in such patients and have a pronounced effect on the likelihood of disease progression, hospital readmission, and mortality. All physicians must be familiar with the principles of cessation practice and be able to initiate smoking cessation attempts.