A large volume of data has accumulated on the issues of tobacco and health worldwide. The relationship between tobacco use and health stems initially from clinical observations about lung cancer, the first disease definitively linked to tobacco use. Almost 35 years ago, the Office of the Surgeon General of the United States Health Service reviewed over 7000 research papers on the topic of smoking and health, and publicly recognized the role of smoking in various diseases, including lung cancer. Since then, numerous studies have been published that substantiate the strong association of tobacco use with a variety of adverse human health effects, most prominently with cancer and cardiovascular diseases. Cigarette smoking is regarded as a major risk factor in the development of lung cancer, which is the main cause of cancer deaths in men and women in the United States and the world. Major advances have been made by applying modern genetic technologies to examine the relationship between exposure to tobacco smoke and the development of diseases in human populations. The present review summarizes the major research areas of the past decade, important advances, future research needs and federal funding trends.