Whether in human, animal, or microbial communities, the resolve to coexist is the quintessence of survival. Therefore, in natural habitats where resources are limited, individual species must collaborate with others in order to survive and endure [1]. Yet even among the highest of species, harmonious coexistence is often elusive, plagued by power struggles, competition, and opportunism. The human mouth with its various niches is an exceptionally complex habitat, harboring unique and diverse microbial communities [2, 3]. In addition to being the initiation point of digestion, the oral microbiome is crucial in maintaining oral health [3–5]. The ecological balance in the oral cavity is maintained through antagonistic as well as mutualistic interspecies interactions [3]. However, perturbations that disrupt the equilibrium of this ecosystem may lead to the overgrowth of species with pathogenic potential and, in turn, the development of oral disease [6]. Although recent advances in molecular biology have facilitated analyses of the oral microbiome, there is a great deal we do not understand about its functions and the processes underlying the transition from a healthy oral microbiome to a disease-associated microbiome. Here, we highlight some of the host and microbial factors orchestrating the ecological balance in the oral cavity, crucial for maintaining a healthy oral microbiome.