Microbial biofilms form on oral surfaces. These biofilms usually exist in dynamic equilibria with host defenses and are compatible with maintenance of the integrity of the target tissues. Disease occurs when the composition and the metabolic activities of complex communities in biofilms are perturbed. These ecologically driven changes in oral biofilms result in increases in the proportions of pathogenic micro-organisms, which possess enzymatic and structural determinants that may render them more virulent than organisms associated with oral health. This brief review focuses on key environmental influences, and genetic and physiologic aspects of bacteria associated with the formation of dental caries, and attempts to identify some areas of oral microbiology in which interdisciplinary efforts will be essential for dissection of the molecular events controlling the development and persistence of pathogenic plaques. The focus is on strategies to enhance fundamental knowledge of oral biofilm composition, structure, and activities, with the rationale that broadly effective therapeutic strategies targeted at plaque physiology, or at biofilm development and persistence, can arise from such knowledge.