The phylum Cnidaria (sea anemones, corals, hydra, jellyfish) is one the most distantly related animal phyla to humans, and yet cnidarians harbor many of the same cellular pathways involved in innate immunity in mammals. In addition to its role in pathogen recognition, the innate immune system has a role in managing beneficial microbes and supporting mutualistic microbial symbioses. Some corals and sea anemones undergo mutualistic symbioses with photosynthetic algae in the family Symbiodiniaceae. These symbioses can be disrupted by anthropogenic disturbances of ocean environments, which can have devastating consequences for the health of coral reef ecosystems. Several studies of cnidarian-Symbiodiniaceae symbiosis have implicated proteins in the host immune system as playing a role in both symbiont tolerance and loss of symbiosis (i.e., bleaching). In this review, we critically evaluate current knowledge about the role of host immunity in the regulation of symbiosis in cnidarians.