In the mid-1970s there were no effective pharmacological treatments for tobacco dependence. The invention of nicotine gum was a major treatment advance and also greatly helped our understanding of the nature of tobacco dependence. There are now eight effective pharmacotherapies (nicotine gum, patch, nasal spray, inhaler, lozenge/tablet, bupropion, nortriptyline and clonidine) available to aid smoking cessation. Other non-nicotine agents that show promise are under investigation, including glucose, rimonabant, selegiline and varenicline. Greater knowledge of the mechanisms of action of the effective non-nicotine agents should lead to better understanding of the nature of tobacco dependence. Future research into optimal treatments should examine long-term combination pharmacotherapy combined with improved psychosocial support that is partly designed to enhance medication compliance. In addition, there is a need for studies designed to evaluate the efficacy of pharmacotherapies in populations such as youth, pregnant smokers and smokers with co-occurring mental health problems.