Biofilms account for more than 60-80% of human infections and continue to remain elusive from the context of theoretical understanding and product development. Within the mouth, soft tissues, and hard tissues as well as prostheses harbor biofilms. Within hard tissues, enamel and dentin are excellent substrates for biofilm adhesion. That said, are all biofilms the same? Should a biofilm on the oral mucosa or enamel be treated the same way as a root canal biofilm? This lecture will provide a conceptual understanding of the similarities and contrasting factors between biofilms that are essential to the etiology of disease that we conservative dentists and endodontists primarily treat.