Sponges form ancient and complex symbiotic interactions with microorganisms. How these interactions are mediated on a molecular level is however poorly understood. Recent (meta-) genomic analyses have uncovered the presence and abundance of genes encoding for eukaryotic-like proteins (ELPs) in microbial symbionts of sponges. Phylogenetic analyses indicate that these ELPs have been horizontally transferred from sponges and other eukaryotes into symbiont lineages. Metatransciptomic analyses showed that a large array of different ELPs is expressed under natural settings, indicating their functional role in symbiosis. Through recombinant approaches it was shown at ELPs can inhibit eukaryotic phagocytosis, which is a relevant phenotype for a symbiont to avoid being consumed by sponge amoebocytes. In fact, Escherichia coli cells, which recombinantly express ELPs from sponge symbionts, were able to persist inside sponges, while E. coli without ELPs were rapidly consumed. For some symbiont ELPs it was also shown that they specifically bind to sponge proteins involved in cytoskeletal formation and cellular regulation. Overall these results support a model whereby microbial symbionts have acquired eukaryotic host genes that have subsequently evolved to function as molecular mediators of symbiotic interactions.