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Tropical corals construct the three-dimensional framework for one of the most diverse ecosystems on the planet, providing habitat to a plethora of species across taxa. However, these ecosystem engineers are facing unprecedented challenges, such as increasing disease prevalence and marine heatwaves associated with anthropogenic global change. As a result, major declines in coral cover and health are being observed across the world's oceans, often due to the breakdown of coral-associated symbioses. Here, we review the interactions between the major symbiotic partners of the coral holobiont—the cnidarian host, algae in the family Symbiodiniaceae, and the microbiome—that influence trait variation, including the molecular mechanisms that underlie symbiosis and the resulting physiological benefits of different microbial partnerships. In doing so, we highlight the current framework for the formation and maintenance of cnidarian–Symbiodiniaceae symbiosis, and the role that immunity pathways play in this relationship. We emphasize that understanding these complex interactions is challenging when you consider the vast genetic variation of the cnidarian host and algal symbiont, as well as their highly diverse microbiome, which is also an important player in coral holobiont health. Given the complex interactions between and among symbiotic partners, we propose several research directions and approaches focused on symbiosis model systems and emerging technologies that will broaden our understanding of how these partner interactions may facilitate the prediction of coral holobiont phenotype, especially under rapid environmental change.