Smoking cessation substantially reduces the risk of cardiovascular disease in the prevention of primary and secondary cardiovascular events. Current first-line therapies include nicotine replacement therapy and bupropion, that approximately double a smoker’s chances of long-term success. Both therapies are safe in patients with cardiovascular disease. Novel treatments include rimonabant, nicotine vaccines and varenicline. To date, varenicline, an a4a2 nicotinic acetylcholine receptor partial agonist has been approved for smoking cessation and has been shown to be efficacious and well tolerated in clinical studies conducted in healthy smokers.