Numerous studies have revealed important functions for sialylation in both prokaryotes and higher animals. However, the genetic and biochemical potential for sialylation in Drosophila has only been confirmed recently. Recent studies suggest significant similarities between the sialylation pathways of vertebrates and insects and provide evidence for their common evolutionary origin. These new data support the hypothesis that sialylation in insects is a specialized and developmentally regulated process which likely plays a prominent role in the nervous system. Yet several key issues remain to be addressed in Drosophila, including the initiation of sialic acid de novo biosynthesis and understanding the structure and function of sialylated glycoconjugates. This review discusses our current knowledge of the Drosophila sialylation pathway, as compared to the pathway in bacteria and vertebrates. We arrive at the conclusion that Drosophila is emerging as a useful model organism that is poised to shed new light on the function of sialylation not only in protostomes, but also in a larger evolutionary context.