Phosphoinositide-specific phospholipase C (PI-PLC) isozymes have an important role in cellular responses to a variety of extracellular signals. Recently, the three-dimensional structures of their isolated domains and of the multidomain core, common to all PI-PLCs, have been solved. This provided an insight into the domain organization of PI-PLCs and, together with the structure-function analysis, contributed towards an understanding of the molecular mechanisms of catalysis and regulation.