As the second largest reservoir of human microbes, the oral cavity is colonized by millions of tiny creatures collectively named as oral microbiome. Species detected in human mouth are diverse, including bacteria, fungi, viruses, and protozoa. Active bidirectional interaction exists between the oral microbiome and the host. Stresses from hosts shape the composition, distribution pattern, and the community behaviors of the oral microbiome, while any changes occurring on the oral microbiome may disrupt its symbiosis relationship with the host and ultimately lead to oral and systemic diseases that jeopardize the host's health. In this chapter, the latest understanding about the role of oral microbiome in common oral diseases, including dental caries, periodontal disease, oral candidiasis, and hyposalivation, is discussed.