The discovery of glycosyl-phosphatidylinositol (GPI) molecules and their products has given new insight into the field of signal transduction. In the last decade a novel mechanism of protein attachment to membranes has emerged, which involves a covalent linkage of the protein to the glycan moiety of a GPI. The discovery that GPI-anchored proteins are ubiquitous throughout the eukaryotes was followed by the observation that uncomplexed GPI molecules are implicated in signal transduction for a diversity of hormones and growth factors. The hydrolysis of free-GPI generates a novel second messenger: the inositol phosphoglycan (IPG). The aim of this article is to review the role of IPG and IPG-like molecules in signal transduction and to discuss future research directions.