Periodontal diseases are infections initiated by specific species of microorganisms and are among the most common human infections. The pathogenesis of periodontitis is mediated by interactions between host and microbial factors, complicated by genetic and environmental risk factors. Periodontal disease also represents a unique model in which to study the roles of bacterial and host-related factors, a model in which patients do not suffer from life-threatening disease. The aim of this paper is to focus on recent findings relating to neutrophil-mediated host response mechanisms in Porphyromonas gingivalis-induced periodontal disease. Virulence factors of Porphyromonas gingivalis such as the gingipains, fimbrillin peptides, capsule polysaccharides, lipopolysaccharides, haemagglutinating and haemolysing activities, toxic products of metabolism, outer membrane vesicles, and other enzymes have important roles in eliciting host responses in various ways. These factors significantly affect epithelial/endothelial cells, but their major effect is observed on the modulation of neutrophil response. Periodontitis represents an important model for neutrophil-mediated host tissue injury. In this model, neutrophils, primed or stimulated by the presence or persistence of infection, express an elevated and excessive response. This, in turn, leads to tissue destruction mediated by neutrophil activity. It is essential to understand the mechanisms underlying the interactions between the neutrophils and the microbial virulence factors to be able to develop rational, novel treatment strategies.