Adequate salivary secretion is crucial to both oral and general health, since it provides a complex milieu for support of the microbial populations of the mouth, while at the same time containing antimicrobial products that help control these microbial populations. This paper summarizes several aspects of salivary component function, gland secretion mechanisms, and immunopathogenesis as related to oral health and disease. Salivary components mediate microbial attachment to oral surfaces, and also interact with planktonic microbial surfaces to facilitate agglutination and elimination of pathogens from the oral cavity. Adhesive interactions are often mediated by lectin-like bacterial proteins that bind to glycan motifs on salivary glycoproteins. An important salivary antimicrobial protein is histatin 5 (Hst 5), which shows potent and selective antifungal activity and also susceptibility to proteolytic degradation. Coupling of Hst 5 with the carrier molecule spermidine significantly enhanced killing of C. albicans and resistance to proteolytic degradation, compared with the parent peptide. Loss of salivary secretion may be caused by disorders such as Sjögren's syndrome (SS) or ectodermal dysplasia, or may be a side-effect of radiation therapy. Two new approaches to the treatment of salivary gland dysfunction include the use of resolvins and the creation of differentiated acinar structures to construct an artificial salivary gland. B-cells contribute to the pathogenesis of SS by releasing cytokines and autoantibodies and by influencing T-cell differentiation. CXCL13, a potent B-cell chemokine associated with autoimmune diseases, is elevated locally and systemically in SS and may represent a novel biomarker or therapeutic target in the management and treatment of SS.