Tobacco use is the leading cause of preventable death and disability in the 
world. Although gradually declining in most developed countries, the prevalence 
of tobacco use has increased among developing countries. Treatment for tobacco 
use and dependence is effective, although long-term abstinence rates remain 
disappointingly low. In response, new treatments continue to be developed. In 
addition, many of the pharmacotherapies that have been available for years have 
found new applications with the use of medication combinations, higher doses and 
a longer duration of therapy for approved medications. There are now seven 
medications (nicotine patch, nicotine gum, nicotine lozenge, nicotine inhaler, 
nicotine nasal spray, bupropion sustained release and varenicline) approved for 
tobacco dependence treatment in most countries, and many national and 
professional society practice guidelines recommend their use. Although each of 
the medications used for tobacco dependence treatment has been rigorously tested 
for efficacy and safety, broader experience in clinical trials and in 
observational population-based studies suggests that adverse events associated 
with these medications are relatively common. Since 2008, two of the medications 
(varenicline and bupropion) have come under increasing scrutiny because of 
reports of unexplained serious adverse events (SAEs), including behaviour 
change, depression, self-injurious thoughts and suicidal behaviour. To date, 
this association has not been shown to be caused by these medications, but 
concerns about medication safety continue. Prescribers require a working 
knowledge of the common adverse effects for all of these medications as well as 
a more detailed knowledge of the SAE potential. Nicotine replacement therapy 
(NRT) has been rigorously tested in clinical trials for over 30 years. A number 
of adverse effects are commonly associated with NRT use, although SAEs are rare. 
The adverse effects associated with NRT are due to the pharmacological action of 
nicotine as well as the mode and site of the NRT application. Bupropion has been 
tested in over 40 controlled clinical trials and has been associated with higher 
rates of treatment discontinuation due to adverse events than NRTs. A number of 
SAEs are associated with bupropion and new warnings were recently added to 
bupropion prescribing information because of observed neuropsychiatric symptoms 
including suicidal thoughts and behaviours. Varenicline is the most recently 
approved medication for tobacco dependence treatment and, although proven safe 
in clinical testing, new safety concerns have arisen based on post-marketing 
reports. Warnings have been added to the prescribing information for varenicline 
because of neuropsychiatric symptoms also including suicidal thoughts and 
behaviours. Informed decision making regarding the use of pharmacotherapy for 
the treatment of tobacco dependence requires knowledge about the risks of drug 
treatment that is weighed against the risks of continued tobacco use and the 
benefits of treatment. Over half of all long-term smokers will die of a 
tobacco-related disease and the risk of a serious or life-threatening adverse 
event with tobacco cessation pharmacotherapy is vanishingly small. 
Pharmacotherapy for tobacco dependence is also among the most cost-effective 
preventive health interventions. Given these factors, the benefit : risk ratio 
is strongly in favour of pharmacotherapy for tobacco dependence treatment in 
virtually all smokers who are motivated to quit.