The human microbiome is receiving a great deal of attention as its role in health and disease becomes ever more apparent. The oral microbiome, perhaps due to the ease with which we can obtain samples, is arguably the most well-studied human microbiome to date. It is obvious, however, that we have only just begun to scratch the surface of the complex bacterial and bacterial–host interactions within this complex community. Here, we describe the factors which are known to influence the development of the seemingly globally conserved, core, oral microbiome and those which are likely to be responsible for the observed differences at the individual level. We discuss the paradoxical situation of maintaining a stable core microbiome which is at the same time incredibly resilient and adaptable to many different stresses encountered in the open environment of the oral cavity. Finally, we explore the interactions of the oral microbiome with the host and discuss the interactions underlying human health and disease.