Problem/Objective: A variety of quit smoking medications or pharmacotherapies have been developed, including nicotine replacement therapy (NRT; nicotine gum, patch, inhaler, nasal spray, and lozenge) and non-nicotine therapies (bupropion and varenicline). The best individual pharmacotherapies for smoking cessation under optimal conditions rarely produce one-year quit rates of more than 25%. Many illnesses such as hypertension and HIV/AIDS often require combination pharmacotherapy (CP) to achieve satisfactory symptom relief and disease control. The purpose of this presentation is to review the published literature on CP for the treatment of nicotine dependence. Methods: CP studies for the present review were identified using three databases, PubMed, PsycINFO, and Web of Science. Queries were conducted employing combinations of NRT and non-NRT pharmacotherapy keywords. Studies included in the present review were those that: (a) compared an NRT/non-NRT to a combination of NRTs or Non-NRTs; (b) had as a primary outcome smoking cessation, (c) were published in peer-reviewed English journals or had been translated into English. Results: A total of 16 CP studies were identified (years 1994–2006). Five trials compared NRT to NRT+NRT, while 11 trials compared NRT to NRT+Non-NRT. Among these trials, only three significant effects favoring CP were found: one trial favoring nasal spray+patch over placebo spray+patch, and two trials favoring mecamylamine+patch to placebo+patch. Conclusions: While the promise of combination pharmacotherapy for smoking cessation remains, the extant literature has shown little benefit in individual studies. Future studies should combine medications with dissimilar mechanisms of action and psychopharmacological effects to maximize quit rates.