The American Indians cultivated tobacco before the arrival of Columbus. They cured the leaves and smoked them in pipes or as cigars, or powdered them for snuff. Some also had a form of cigarette in which the tobacco was put into reeds fitted with mouthpieces. The Indians believed that tobacco cured various diseases. Pipe smoking was often part of religious and social ceremonies.

Spanish settlers in the West Indies began cultivating N. rustica in the 1530's and exporting it to Europe before the end of the 16th century. Jean Nicot, a French diplomat, introduced the use of tobacco to the French court in the 1560's. The tobacco genus was named in his honor. Sir Walter Raleigh was instrumental in popularizing smoking in England during the latter half of the 16th century. By the early 1600's, tobacco had been introduced into Asia, Africa, and Australia.

Commercial cultivation of N. tabacum was begun by John Rolfe in Virginia in 1612, and tobacco rapidly became the most important export of the colonies. N. tabacum quickly replaced N. rustica in commercial production because of its milder flavor and aroma. After the Revolutionary War, the domestic manufacture of tobacco products became important in the United States.

While some people believed that tobacco had medicinal effects, its use was opposed by others on the grounds of health and morals from the time it was introduced into Europe. James I of England and Pope Urban VIII tried to discourage smoking, and in the New England colonies in the 18th century, attempts were made to ban it. During the 19th and the early 20th century, many Protestant churches in the United States vigorously attacked the use of tobacco. Opposition on medical grounds became pronounced beginning in the 1960's. According to the U.S. Centers for Disease Control and Prevention, the percentage of adults who smoke cigarettes declined in the United States from about 42 in 1965 to about 23 in 1997.

In 1996, President Bill Clinton announced a broad-based health initiative intended to reduce smoking by young people. His provisions included a requirement were a requirement that merchants verify with photo identification the age of young purchasers of tobacco products, and restrictions on tobacco marketing that is appealing to children and teenagers.

In the mid-1990's, tobacco companies became the target of lawsuits by individuals and states seeking damages for health problems caused by smoking. Forty states sued tobacco companies to recover Medicaid costs of tobacco-related illnesses. In 1998, the tobacco industry and states reached a historic agreement that required manufacturers to reimburse states $26 billion over a period of 25 years for these medical costs. In addition, tobacco companies were required to participate in anti smoking campaigns.

The genus Nicotiana belongs to the nightshade family, Solanaceae.