Smoking cessation is the single most effective behavioral change for disease prevention. While almost 20% of the US population smokes, 70% of these smokers indicate they would like to quit. However, only approximately 3-5% of smokers quit without the aid of some intervention. Best practice suggests that every patient who smokes is offered brief behavioral counseling with pharmacotherapy support for smoking cessation. The past decade has presented new pharmacotherapies for tobacco cessation that allow the clinician more options for individualizing therapy to maximize each patient's chance for tobacco abstinence. Nicotine replacement therapy, bupropion sustained release and varenicline are discussed as monotherapies and in combination. As the understanding of neuropharmacology increases and new pharmacotherapies are developed, there will be the possibility of tailoring therapies for individual patients based on genetic predispositions and other individual characteristics. © 2009 Expert Reviews Ltd.