The use of chlorhexidine for caries prevention has been a controversial topic among dental educators and clinicians. In several reviews, it has been concluded that the most persistent reduction of mutans streptococci have been achieved by chlorhexidine varnishes, followed by gels and, lastly, mouth rinses. Also, the evidence for using different chlorhexidine modes or a combination of chlorhexidine-fluoride therapy for caries prevention has been "suggestive but incomplete". Variable study designs and lack of data in high-risk children and adults support the need to continue conducting randomized, well-controlled clinical trials and to search for a practical, effective mode of antimicrobial treatment that augments the known effect of fluoride treatments. Currently, the only chlorhexidine-containing products marketed in the United States (US) are mouthrinses containing 0.12 percent chlorhexidine. Based on the available reviews, chlorhexidine rinses have not been highly effective in preventing caries, or at least the clinical data are not convincing. Due to the current lack of long-term clinical evidence for caries prevention and reported side effects, chlorhexidine rinses should not be recommended for caries prevention. Due to the inconclusive literature and sparse clinical data on gels and varnishes, their use for caries prevention should also be studied further to develop evidence-based recommendations for their clinical role in caries prevention. Since dental caries is a disease with a multifactoral etiology, it is currently more appropriate to use other established, evidence-based prevention methods, such as fluoride applications, diet modifications and good oral hygiene practices. Recent findings also indicate that the effect of an antimicrobial agent for reducing the levels of mutans streptococci or plaque reduction may not always correlate with eventual caries reduction. The clinically important outcome is proven reductions in caries. Many advances in the treatment and prevention of dental caries have been introduced over the past century. The use of chlorhexidine in caries prevention has been referred to as a nonsurgical management of dental caries and has represented the modern medical model of caries treatment. However, there is a lack of consensus on evidence-based treatment protocols and controversy regarding the role of chlorhexidine in caries prevention among dental educators and clinicians. There is a need to standardize guidelines to optimize evidence-based non-surgical disease management to provide appropriate care. This paper reviewed the literature on the effectiveness of different modes of chlorhexidine delivery for caries prevention and provides guidelines for chlorhexidine use in caries management. A literature search was conducted using the PubMed and Evidence-Based Medicine Reviews databases and the keywords "chlorhexidine" and "caries", limiting the search to "humans", "reviews" and "English". Based on the published reviews, it was concluded that chlorhexidine rinses, gels and varnishes or combinations of these items with fluoride have variable effects. Additionally, the sparse clinical data that was reported weakens the conclusions. Due to the current lack of evidence on long-term clinical outcomes and reported side effects, chlorhexidine rinse, which is currently the only treatment mode available in the US, should not be recommended for caries prevention. Clinical evidence on gels and varnishes is also inconclusive. For the treatment of dental caries, there are alternative evidence-based prevention methods available, such as fluoride applications, diet modifications and good oral hygiene practices.