Animals evolved in a world teeming with microbes, which play pivotal roles in their health, development, and evolution. Although the overwhelming majority of living animals are invertebrates, the minority of “microbiome” studies focus on this group. Interest in invertebrate-microbe interactions is 2-fold—a range of immune components are conserved across almost all animal (including human) life, and their functional roles may be conserved. Thus, understanding cross talk between microbes and invertebrate animals can lead to insights of broader relevance. Invertebrates offer unique opportunities to “eavesdrop” on intricate host-microbe conversations because they tend to associate with fewer microbes. On the other hand, considering the vast diversity of form and function that has evolved in the invertebrates, they likely evolved an equally diverse range of ways to interact with beneficial microbes. We have investigated only a few of these interactions in detail; thus, there is still great potential for fundamentally new discoveries.