With the evolution of multicellularity in the Metazoa came the critical need for communication among and between different cell populations to coordinate the myriad of cellular activities found within individual organisms. Many of these activities are associated with normal developmental processes or morphogenesis, and are regulated by ”self”-recognizing cellular adhesion molecules. In the vertebrate immune system, however, cell adhesion molecules take on added roles, not only in mediating interactions with ”self”, but also in ”nonself” recognition and elimination of infectious agents, foreign bodies or damaged/transformed cells. Although the structure and function of cell adhesion receptors and their signaling pathways involved in immune functions in the vertebrates have been extensively studied, it is within the diverse group of invertebrate animals that the origins of these receptors may be found, and about which relatively little is known. In this review, we discuss the current state of knowledge regarding immune adhesion molecules in invertebrates, especially those associated with circulating blood cells or hemocytes, and draw parallels to similar families of molecules present in vertebrate immunocytes. The groups to be considered here comprise several families of cellular adhesion molecules including the lectins, integrins, and those of the immunoglobulin superfamily. By comparing the structure and function of adhesion molecules of vertebrates and invertebrates, we hope to provide a better understanding of the possible origins of these molecules and how their function in internal defense is shared across a wide phylogenetic spectrum.