Periodontitis is an infection-driven inflammatory disease, which is characterized by gingival inflammation and bone loss. Periodontitis is associated with various systemic diseases, including cardiovascular, respiratory, musculoskeletal, and reproductive system related abnormalities. Recent theory attributes the pathogenesis of periodontitis to oral microbial dysbiosis, in which Porphyromonas gingivalis acts as a critical agent by disrupting host immune homeostasis. Lipopolysaccharide, proteases, fimbriae, and some other virulence factors are among the strategies exploited by P. gingivalis to promote the bacterial colonization and facilitate the outgrowth of the surrounding microbial community. Virulence factors promote the coaggregation of P. gingivalis with other bacteria and the formation of dental biofilm. These virulence factors also modulate a variety of host immune components and subvert the immune response to evade bacterial clearance or induce an inflammatory environment. In this chapter, our focus is to discuss the virulence factors of periodontal pathogens, especially P. gingivalis, and their roles in regulating immune responses during periodontitis progression.