This article discusses the evolution of smokeless tobacco in the United States and interprets the available data on cardiovascular risk factors and cardiovascular mortality associated with its use. There has been a resurgence of smokeless tobacco use since 1970. Smokeless tobacco consistently produces levels of nicotine higher than those seen with smoking and causes similar sympathetic neural stimulation and acute cardiovascular effects. However, there is conflicting evidence from prospective and case-control studies about cardiovascular mortality or myocardial infarction caused by smokeless tobacco use. Smokeless tobacco use is also associated with oral cancers and high-risk behavior in adolescents. Although the evidence is not conclusive, the adverse cardiovascular effects of smokeless tobacco use are less than those caused by smoking but are more than those found in nonusers. It is advisable to counsel all current users of smokeless tobacco to quit. Behavioral counseling, sustained-release bupropion hydrochloride therapy, and nicotine replacement therapy may be safe therapeutic modalities for treatment of smokeless tobacco use.