The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth. The susceptibility to periodontitis appears to be determined by the host response; specifically, the magnitude of the inflammatory response and the differential activation of immune pathways. The purpose of this review was to delineate our current knowledge of the host response in periodontitis. The role of innate immunity, the failure of acute inflammation to resolve (thus becoming chronic), the cytokine pathways that regulate the activation of acquired immunity and the cells and products of the immune system are considered. New information relating to regulation of both inflammation and the immune response will be reviewed in the context of susceptibility to, and perhaps control of, periodontitis.