The control of potentially periodontopathic microorganisms by host neutrophils is crucial to periodontal health. Neutrophils may use oxidative or nonoxidative mechanisms and either kill bacteria, influence bacterial growth, or modify bacterial colonization in the periodontium. Delivery of antimicrobial substances by neutrophils involves respiratory burst activity, phagocytosis, secretion, or cytolysis/apoptosis. Neutrophils contain a number of antimicrobial components including calprotectin complex, lysozyme, defensins, cofactor-binding proteins, neutral serine proteases, bactericidal/permeability increasing protein, myeloperoxidase, and a NADPH oxidase system. Many of these components are multifunctional and exhibit several mechanisms of antimicrobial activity. When comparisons are made among periodontal bacteria, differences in sensitivity to different components are observed. A hypothesis of specific defense is presented: That specific periodontal diseases can result from the failure of specific aspects of the host immune system (the neutrophil, in particular) in its interaction with specific periodontal pathogens. Failure may be due to phenotypic variation (pleomorphism) within the host or bacterial evasive strategies.