Biofilms are collections of microorganisms at interfaces. Because of the high proportion of interfacial regions in the natural environment, biofilms are likely to be the repository for most of the world's microbial biomass. The close proximity of organisms within the biofilm presents the opportunity for intra- and interspecies signaling on a physical level through direct contact of organisms with one another, and on a metabolic level through production/excretion of intermediary molecules of metabolism and of specific cell signaling molecules. One of the best studied biofilms is dental plaque, which has been investigated from a microscopy standpoint since the time of van Loewenhouk and from a classical bacteriological standpoint since the relatively recent (20th century) development of anaerobic culture techniques. Through the even more recent (the last decade) application of molecular methods, it has been shown that perhaps half of all bacteria present in plaque are culturable and, at present, this consists of some 500 species.