Dental plaque, a microbial biofilm that accumulates on teeth and initiates periodontal disease, is composed of hundreds of different bacterial species within an organized structure. The biofilm bacteria and their byproducts irritate the gingival epithelium and induce an "inflammatory response". The perturbation of epithelial cells by bacteria is the first stage in the initiation of inflammatory and immune processes which eventually cause destruction of the tissues surrounding and supporting the teeth, and ultimately result in tooth loss. This review addresses the early bacterial-epithelial cell interactions and the subsequent responses of the epithelial cell. It includes discussion of how epithelial Toll-like receptors (TLRs) respond to different bacterial challenges, the variable antimicrobial peptides released and the host signaling responses which trigger release of these molecules and the overall fate of these cells in terms of survival, apoptosis, or cell lysis.