Based on the assumption that invertebrates as well as vertebrates possess factors regulating hematopoiesis, response to infection or wounding, studies dealing with the evolution of immunity have focused on the isolation and characterization of putative cytokine-related molecules from invertebrates. Until recently, most of our knowledge of cytokine- and cytokine receptor-like molecules in invertebrates has relied on functional assays and similarities at the physicochemical level. As such, a phylogenetic relationship between invertebrate cytokine-like molecules and invertebrate counterparts could not be convincingly demonstrated. In the present book, recent studies demonstrating cytokine-like activities and related signaling pathways in invertebrates are critically reviewed, focusing on findings from molecular biology and taking advantage of the completion of the genome from the fly Drosophila and the worm Caenorhabditis elegans.