This chapter reviews the principles of systems biology and their application through computational methods (bioinformatics, computational biomodeling, genomics, proteomics, oral human microbiome, molecular modeling, systems biology, protein structure prediction, structural genomics, computational biochemistry and computational biophysics methods and projects) that have been applied to oral diseases research. The emphasis of the chapter is on concepts from molecular biology, genetics, and traditional pathology to provide new insights into oral diseases, and the associated technologies to provide new diagnostic, therapeutic and prognostic information. Another goal of the manuscript will be to serve as a central reference to access of information about systems biology resources for research into oral diseases.