In the natural environment animal tissues harbor diverse communities of microbes. Increasing evidence suggests these communities are shaped by host-selection and provide beneficial functions including nutrient cycling and pathogen protection. How such tissue-specific microbial communities are assembled and maintained remains a central question for understanding the role of microbes in health and disease. The starlet sea anemone Nematostella vectensis is emerging as a model for animal development and evolution because the phylum Cnidaria is one of the earliest branches on the animal tree of life. In addition, N. vectensis is closely related to corals and is a tractable laboratory model for probing the mechanisms of disease and disease resistance in the class Anthozoa.