The tobacco smoke formation from a burning cigarette is the result of a complex physico-chemical process. Two distinct zones can be identified in the burning coal. The first one is the combustion zone where the oxygen from the incoming air is still present. Mainly, Exothermic oxidation reactions are observed in this zone. The second one is the pyrolysis-distillation zone which is oxygen depleted. Endothermic degradation reaction are predominant here. Most of the non volatile compounds are generated in the pyrolysis-distillation zone, whereas the gaseous compounds are formed in both zones but at a higher temperature. As the chemical composition of tobacco is already complex, this formation process generates several thousand compounds in tobacco smoke. They form an aerosol which is composed of a particulate phase (small particles) dispersed in a gaseous phase. There is no validated theory describing the toxicity of tobacco smoke which appears to be multifaceted. Using the IARC classification, it is possible to list the potentially carcinogenic compounds present in tobacco smoke. The main categories are the polycyclic aromatic hydrocarbons, the tobacco specific nitrosamines, the aromatic amines, the heterocyclic aromatic amines, some volatile compounds (aldehydes, unsaturated hydrocarbons, and phenols) and the heavy metals. In general, the levels of these compounds in smoke are too low to explain the observed toxicity and synergistic effects are probably occurring. The development of methodologies allowing a more sensible and more specific detection of "biologically active" compounds, could result in a better understanding of the smoke toxicity mechanisms in relationship with its chemical composition. Then it would be possible to engage strategies of smoke toxicity reduction based on selective removal or reductian of the relevant compounds.