Corals are fundamental ecosystem engineers, creating large, intricate reefs that support diverse and abundant marine life. At the core of a healthy coral animal is a dynamic relationship with microorganisms, including a mutually beneficial symbiosis with photosynthetic dinoflagellates (Symbiodinium spp.) and enduring partnerships with an array of bacterial, archaeal, fungal, protistan, and viral associates, collectively termed the coral holobiont. The combined genomes of this coral holobiont form a coral hologenome, and genomic interactions within the hologenome ultimately define the coral phenotype. Here we integrate contemporary scientific knowledge regarding the ecological, host-specific, and environmental forces shaping the diversity, specificity, and distribution of microbial symbionts within the coral holobiont, explore physiological pathways that contribute to holobiont fitness, and describe potential mechanisms for holobiont homeostasis. Understanding the role of the microbiome in coral resilience, acclimation, and environmental adaptation is a new frontier in reef science that will require large-scale collaborative research efforts.