Tobacco use remains the major preventable cause of early mortality and morbidity in the US and is a major risk factor for cardiovascular disease (CVD). Quitting smoking rapidly reduces the risk of cardiovascular events. In this review, we identify and discuss best approaches to assist smoking cessation among patients with CVD. Establishing office systems that reliably identify smokers to healthcare providers is an essential first step. Once the patient is identified as a smoker, providers should inquire about their willingness to quit and advise them to quit or provide motivation to get ready to make a quit attempt. Behavioral (counseling) and pharmacologic (nicotine replacement and non-nicotine medications) treatments double or triple long-term cessation rates and should be offered in combination to all patients with CVD who use tobacco. More intensive behavioral therapy is more effective and should be delivered when possible. The choice of pharmacotherapy will depend upon the clinical history of the patient and patient preference. Nicotine replacement and sustained release bupropion (bupropion SR) are first-line treatments for smoking cessation. Nicotine patches have been studied extensively in patients with stable CVD and have been shown to be safe. Bupropion SR has relatively few cardiovascular adverse effects and may be especially useful for patients with CVD; its safety is currently being studied. Special consideration is needed for hospitalized patients with acute coronary syndromes (e.g. myocardial infarction and unstable angina). The safety of pharmacotherapy in the acute setting is not yet established. Behavioral interventions, however, are very effective and should be delivered to all hospitalized smokers. Finally, it is important to create a clinical environment that is supportive of treating patients with tobacco dependence. Simple changes in office and hospital routines and procedures (routine screening to identify smokers, prompts to encourage intervention and links to more intensive tobacco dependence treatment programs) will substantially improve the identification, treatment, and outcomes of patients with CVD who use tobacco.