Dental caries is an infectious disease of bacterial origin. The use of antimicrobial agents to reduce or eliminate the bacteria associated with caries follows the approach used to combat other infectious diseases of humans. Unfortunately, only a few dozen studies have sufficient resolving power to make inferences as to the anticaries efficacy of the antimicrobial approach to caries management. Here, we comment on the findings of the RTI/UNC review concerning antimicrobials, discuss additional findings not covered in that review, and make recommendations based upon both the available literature and from our own experience. Even though the studies published thus far are inconclusive or lack sufficient demonstration of efficacy to recommend a specific approach involving antimicrobial agents in routine clinical practice, several pieces of information from these studies suggest future avenues of investigation.