Purpose: To evaluate the association between chlorhexidine application and the bond strength of an adhesive system to dentin and to assess the association among eight other variables. Materials and Methods: Laboratory studies evaluating the use of chlorhexidine on dentin that verified the immediate and longitudinal bond strength were included. The terms were selected according to the Medical Subject Headings (MeSH) for PubMed and adapted for the other databases accordingly. Systematic searches were conducted in 3 electronic databases in December 2010: PubMed, EMBASE, and LILACS. Languages were limited to English, Spanish, and Portuguese. Results: All longitudinal bond strength studies were analyzed in accordance with the inclusion/exclusion criteria, totaling 16 articles. A meta-regression analysis was performed with articles containing complete mean bond strength data (n = 14 articles). Conclusion: Our results showed that the association between the concentration of chlorhexidine and the bond strength is, apparently, not linear. Therefore, future large-scale studies should be developed to investigate the association between the chlorhexidine concentration and hybrid layer preservation. Keywords: adhesive, dentin, matrix metalloproteinases