Dental plaque is a complex biofilm with a high clinical relevance, resulting from the accumulation and interaction of oral microorganisms attached to a tooth surface. The two major oral diseases, dental caries and periodontal disease, are derived from a dysbiosis of the oral microbiome. Moreover, other important diseases such as Alzheimer’s disease and oral cancer have been related to oral diseases. The high cell density achieved within the biofilm matrix is an optimal environment for the occurrence of bacterial chemical communication processes known as quorum sensing. Although it is known that this cell-to-cell communication is required for biofilm development of many pathogenic bacteria, including the successful establishment of biofilms of most relevant oral pathogens, knowledge of the microbial interactions and signaling processes within poly-microbial oral biofilms is still limited. This review is an effort to encompass the current knowledge on the role of quorum sensing systems in oral biofilm formation and how the inhibition of these processes could constitute a potential approach to prevent and treat infectious diseases.