Smoking is recognized as a chronic and recurrent addictive disease. It is the leading preventable cause of death in the world and kills 4 million people worldwide annually. Because of the high morbidity and mortality associated with tobacco use and the substantial benefits of cessation, it is vital that all physicians encourage their patients who smoke to quit and assist in their smoking cessation attempts. According to the United States Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence: “smoking cessation treatment should include a combination of pharmacotherapy, to relieve the smoker's dependence on nicotine, as well as psychologic support to combat the smoker's addiction to inhaled tobacco consumption.” This review discusses the rationale behind the use of pharmacotherapy for smoking cessation and the recommended first- and second-line therapies. It also focuses on the new medication for smoking cessation: varenicline.