Promoting smoking cessation is among the key medical interventions aimed at reducing worldwide morbidity and mortality in this century. Both behavioural counselling and pharmacotherapy have been shown to significantly increase long-term abstinence rates, and combining the two treatment modalities is recommended. This article provides an update on pharmacotherapy for smoking cessation in the general population. Current first-line agents used to support quit attempts are nicotine replacement therapy (NRT), bupropion and varenicline. Research suggests that abstinence rates can be increased by combining different forms of NRT or simultaneously administering NRT and non-nicotine medications. New treatments targeting the nicotinic acetylcholine receptor as well as other pathophysiological pathways involved in nicotine addiction are being developed, with nicotine vaccines now being tested in phase III clinical trials. Among the numerous research topics currently addressed, pharmacogenetics and tailoring therapy to specific groups of smokers look most promising. However, substantial progress is unlikely to be made unless social gradients impeding effective treatment of all smokers are overcome. In addition, public smoking bans and reimbursement of medication costs are crucial in reducing the future burden of disease caused by smoking on a global level.