In this review we presented a relation between cigarette smoking and lung cancer. We characterized molecular alterations resulting from carcinogens present in the cigarette smoke and presented the constitutive genetic profiles related to the increased risk of lung cancer. We also discussed a possible use of these profiles in the selection of high risk groups among the heavy smokers. Finally, a positive impact of quitting smoking in lung cancer patients, including those who have undergone curative resection, was presented.