The human oral flora is normally composed of hundreds of different types of bacteria. This high degree of complexity is largely responsible for the observation that a state of health is the predominant condition of the oral cavity: Myriad bacterial interactions between innocuous and potentially pathogenic species prevent the latter from attaining sufficient numbers to initiate clinically observable diseases. However, protracted or profound perturbations of the oral environment may lead to ecological upsets fundamentally characterized by extreme simplification of the resident flora. Radiation- or autoimmune-induced xerostomia is a striking example of such a perturbation. During the period of floral simplification, as the bacterial interactions diminish, impediments to the outgrowth of pathogens are lost, ultimately leading to the onset of disease. In the absence of methods to reverse the conditions responsible for the ecological upset, as is currently the case in many forms of xerostomia, the possibility of restoring a complex, balanced flora is not imminently practical. However, as our understanding of microbial ecology and pathogenesis develops, application of a replacement therapy approach may become plausible to prevent or retard particular diseases prevalent in xerostomia patients.