Group of microorganisms that reside at particular surfaces of the body is referred to as the normal or commensal flora. The interaction between the commensal normal flora and its host is considered as an ecosystem. The topographical arrangement of the oral cavity with its varied terrain of teeth, gingival crevices or pockets, buccal and lingual sulci, lips and tongue has great influence on the physical parameters of bacterial colonization. Microflora of oral cavity consists of various bacteria like rods, cocci, aerobic, and anaerobic. About 90% of streptococci have been found in plaque and isolated. Neisseria species are common isolates in the mouth and are characteristically aerobic or facultative, oxidase positive, Gram-negative proportion of the organisms. Viruses are mainly classified by phenotypic characteristics, such as morphology, nucleic acid type, mode of replication, host organisms, and the type of disease they cause. Clinical presentation of common oral viral infections like herpes simplex virus, coxsackievirus, verruca vulgaris, human immunodeficiency virus and acquired immune deficiency syndrome, and hepatitis are given in this chapter.