The colonization of freshwater habitats by marine-adapted organisms represents a major transition that has only occurred a few times in the evolution of animals. Only around half of the extant animal phyla have representatives in both marine and freshwater environments and even within those phyla some major clades are restricted to marine environments. Moving from marine to freshwater environments can create severe osmotic and ionic stresses and the mechanisms that animals have used to adapt to those stresses are still not well understood. In this study, we downloaded amino acid sequence data from 11 spiralian animal genomes (four freshwater taxa representing four different phyla as well as 7 marine taxa) and identified a number of gene family expansions that have occurred exclusively in the freshwater lineages. Further investigation of these gene families and the timing and nature of their expansions will illuminate one of the major evolutionary transitions in the history of life on Earth.