The gram-negative anaerobic bacterium Porphyromonas gingivalis has been strongly associated with the causation of human periodontal diseases. One distinguishing property of these organisms that has been implicated in periodontal destruction is the expression of potent protease activity. Recent biochemical and genetic approaches have clearly demonstrated that at least five distinct proteases are elaborated by these organisms. The utilization of monospecific mutants defective in individual proteases has demonstrated that protease activity is important in virulence but also has suggested the complexity of the functions of the enzymes in the physiology of these microorganisms. This review summarizes current progress in assessing the role of these enzymes in periodontal inflammation and discusses some unresolved issues relevant to the significance of P. gingivalis proteases in virulence.