Nicotine addiction and the neurobiological mechanisms explaining nicotine reinforcement, withdrawal, and relapse involve alpha4beta2 nicotinic acetylcholine receptors (nAChRs). This review updates readers on the preclinical and clinical pharmacology, as well as the therapeutic efficacy and safety of cytisine and varenicline, the two partial agonists of nAChRs for smoking cessation. Cytisine has been used for several decades; yet despite its surprising popularity in some parts of the world, it has been absent from almost all existing reviews of smoking cessation drugs. If safe and sufficiently efficacious, an obvious advantage would be its low cost, which could make cytisine an attractive treatment available to millions of smokers. Varenicline was recently introduced to the drug market and has been found to be more efficacious than existing treatments. Very encouraging results of early human trials and strong theoretical background for their use make the nAChRs partial agonists a promising alternative for currently available antismoking treatments.