Objective: To evaluate the effectiveness of chlorhexidine mouthwashes on the reduction of cariogenic bacteria on patients with moderate to high risk for dental caries. Data Sources: A systematic review of the literature was performed using Cochrane Library, Embase, PubMed, Scopus and Web of Science. The search was limited to articles in English, Spanish, and Portuguese, published until January 2017. The research question was formulated following the PICO strategy. The risk of bias was evaluated using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. Conclusion: All the authors found statistically significant differences in Streptococcus mutans levels during and after the use of a chlorhexidine mouthwash. Although the results are suggestive, there is a clear need for the development of new studies with higher quality and with longer follow-ups, in order to assess whether the results translate into less development of dental caries and, consequently, whether or not these products should be incorporated into prevention protocols. Keywords: chlorhexidine, dental caries, Lactobacillus, mouthwashes, prevention, Streptococcus mutans