Smoking is associated with different serious diseases, including cancer. The fact that only a minority of smokers develops tobacco-associated diseases suggests the contribution of other individual factors, which are still far from understood. New technologies that can be referred to as 'molecular profiling' allow for investigating the deregulation of thousands of genes simultaneously. Numerous such studies have investigated in vitro and in vivo the effects of smoking in different cell types aiming at a better understanding of smoking-induced diseases and the detection of new biomarkers of exposure and harm. This review is a short survey of these investigations and how they have contributed to the detection of new biomarkers and to a better understanding of smoking-induced harm.