Despite the abundance of evidence linking tobacco consumption to many oral conditions, no systematic review of the relationship with dental caries is available. The main aim of this systematic review was, therefore, to evaluate the effect of tobacco smoking on dental caries in adult smokers. According to the PRISMA checklist, observational studies published from January 1991 to June 2011 were reviewed. The quality of evidence for each finding was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Five studies, four related to dental caries and one on oral bacteria activity, were finally included in a qualitative analysis; they were all cross-sectional studies. As a result, the overall quality of evidence was poor, with two articles given a score of very low and three a score of low according to GRADE. Tobacco smoking was found to be associated with an increased risk of dental caries. However, the overall poor quality of studies produced no validation for such an association. Further, more extensive research on this topic and prospective studies are needed.