Tobacco was introduced into Europe from America at the end of the fifteen century. At first used primarily for medicinal purposes it came to be burnt in pipes for pleasure on a large scale nearly 100 years later, at first in England and subsequently in Europe and throughout the world. Pipe smoking gave way to the use of tobacco as snuff and, in turn, to cigars and cigarettes at different times in different countries until cigarette smoking became the dominant form in most of the developed world between the two world wars. Societies were formed to discourage smoking at the beginning of the century in several countries, but they had little success except in Germany where they were officially supported by the government after the Nazis seized power. In retrospect it can now be seen that medical evidence of the harm done by smoking has been accumulating for 200 years, at first in relation to cancers of the lip and mouth, and then in relation to vascular disease and cancer of the lung. The evidence was generally ignored until five case-control studies relating smoking to the development of lung cancer were published in 1950. These stimulated much research, including the conduct of cohort studies, which, by the late 1950s, were beginning to show that smoking was associated with the development of many other diseases as well. The interpretation that smoking caused these various diseases was vigorously debated for some years but came to be generally accepted in respect of lung cancer by the late 1950s and of many other diseases in the subsequent two decades. Cigarette smoking has now been found to be positively associated with nearly 40 diseases or causes of death and to be negatively associated with eight or nine more. In some instances the positive associations are largely or wholly due to confounding, but the great majority have been shown to be causal in character. The few diseases negatively associated with smoking are for the most part rare or nonfatal and their impact on disease incidence and mortality as a result of smoking is less than 1% of the excess of other diseases that are caused by smoking. The most recent observations show that continued cigarette smoking throughout adult life doubles age-specific mortality rates, nearly trebling them in late middle age. All the diseases related to smoking that cause large numbers of deaths should now have been discovered, but further nonfatal diseases may remain to be revealed by cohort studies that are able to link individuals' morbidity data with their personal characteristics.