Antimicrobial agents, delivered either by mouthrinse or toothpaste, can be used to maintain plaque at levels compatible with oral health by (a) reducing existing plaque, (b) preventing the formation of new plaque, (c) selectively inhibiting those particular bacteria that are associated with disease, and (d) inhibiting the expression of virulence determinants. Although many antimicrobial agents would appear to be suitable for plaque control, few have been found to possess clinical efficacy. This is because of inherent problems in the mode of action of agents in the mouth, and with difficulties with their formulation into dental products. Currently formulated antimicrobial agents include metal salts (e.g., zinc, stannous, copper), phenols (triclosan), plant extracts (sanguinarine), enzymes (e.g., glucanase, amyloglucosidase/glucose oxidase), “essential oils” (e.g., thymol, menthol), and bisbiguanides (chlorhexidine). Although many of these agents exhibit a broad spectrum of antimicrobial activity in the laboratory, they may display valuable selective properties on plaque. The effect of an agent will be concentration-dependent. Initially, the inhibitor may be briefly at levels above its MIC, but thereafter, it will be desorbed off oral surfaces and operate at sub-lethal concentrations. At these latter levels, agents can be effective by inhibiting metabolism (e.g., acid production, protease activity), and slowing bacterial growth. Agents with complementary modes of action are being combined to increase their antibacterial effectiveness. The long-term use of dental products containing antimicrobial agents should not (a) disrupt the natural balance of the oral microflora, (b) lead to colonization by exogenous organisms, or (c) lead to the development of microbial resistance. Several products are now available that satisfy these criteria, and are clinically effective in helping to control plaque and gingivitis.