Smoking, the most prominent nongenetic factor contributing to mortality, remains the major public health problem throughout the world. There are nearly 1.1 billion users of nicotine and tobacco products worldwide while approximately one third to half of them will die from smoking-related disease. The habit of smoking is mainly propelled by nicotine, a strongly addictive substance, to which the vast majority of smokers fall victim. Except for the general and specific support and counseling strategies there are now effective treatments for nicotine addiction. Two types of pharmacological therapies have been approved and are now licensed for smoking cessation. The first therapy consists of nicotine replacement, substituting the nicotine from cigarettes with safer nicotine formulations. The second therapy is bupropion, an antidepressant of the aminoketone class, which has been demonstrated to be effective in smoking cessation. However, although some cigarette smokers are able to quit, many are not, and standard medications to assist smoking cessation are ineffective. Several agents used for other indications (e.g. neurological diseases, depression, alcoholism) might be used to treat this subgroup. In conclusion, new more effective drugs are needed in order to fight the panepidemic of smoking globally.