The complexity of the oral environment, and ethical problems associated with studies of oral diseases in humans inevitably directed the attention to development of laboratory models, that simulate the human oral microcosm. These developments and in particular the in vitro 'artificial mouth' systems have progressed from simple and basic apparatus devised by Magitot and Miller at the end of 19th century to the currently available, highly sophisticated, computer-controlled, multi-station artificial mouth systems. These advances have metamorphosed from the early studies devised primarily to investigate factors affecting the carious process to the present designs that evaluate growth, pathogenicity, metabolism and mineralization of dental plaque under highly controlled conditions. The modern 'artificial mouth systems' can evaluate microbial interactions in simulated dental plaque and similar biofilms and monitor their physical, chemical, biological and molecular features to a very high degree of accuracy. We review and trace here the historical aspects and developments leading to the currently available artificial mouth systems and discuss their contribution to the study of oral flora, especially related to many variants of dental caries.