In the human oral cavity, which is an open growth system, bacteria must first adhere to a surface in order to be able to colonize. Ability to colonize a non-shedding tooth surface is necessary prior to any odontopathic or periodontopathic process. Complex microbe-host relationships occur and must be studied before the commensal-to-pathogenic nature of the human indigenous oral flora can be understood. Medical pathogens, if present in the appropriate host, always produce specific disease. Caries and periodontal diseases are conditional diseases, requiring numbers of certain indigenous species at various sites, particularly the tooth surface. In the case of caries, the condition is related to sugar consumption. Periodontal disease/s may require certain host and environmental conditions, such as local environment or nutritional factors in gingival crevicular fluids. Nonetheless, critical numbers of certain indigenous species must be present in order for these diseases to occur. The aim of this review is to understand the acquisition of the indigenous oral flora and the development of human dental plaque. The role of the salivary pellicle and adherence of indigenous bacteria to it are critical first steps in plaque development. Bacterial interactions with saliva, nutritional factors, growth factors and microbial physiologic processes are all involved in the overall process of microbial colonization.