Background: Smokeless tobacco (ST) substitution for cigarettes as a method to reduce harm has been actively debated. Use of ST as a smoking cessation method or as a means to reduce cigarettes has been proposed. The impact of using ST in these ways is relatively unknown. Method: A review of the different issues and studies related to using smokeless tobacco as a method to reduce tobacco toxin exposure and harm is presented. Results: The toxicity of the product itself varies by brand of ST and across countries. Of the existing studies, comparisons of consequences between cigarettes and ST show that cigarette smoking produces more negative health effects, is likely to have a higher addiction potential and more severe withdrawal, and leads to a higher rate of relapse than ST use. On the other hand, ST use facilitates the use of cigarettes, which is a deadly tobacco product. Additionally, ST is not a harmless product, and a less harmful product, medicinal nicotine, is available as an effective treatment approach. Furthermore, ST products are not under the same regulatory scrutiny as medicinal nicotine products. Conclusions: Considerably more research and product regulation is necessary prior to considering smokeless tobacco as a harm reduction method.