Phospholipases are important enzymes in cell signal transduction since they hydrolyze membrane phospholipids to generate signalling molecules. Heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins) play a major role in their regulation by a variety of agonists that activate receptors with seven membrane-spanning domains. Phospholipases of the C type, which hydrolyze inositol phospholipids to yield inositol trisphosphate and diacylglycerol, are regulated by the alpha and betagamma subunits of certain heterotrimeric G proteins as well as by receptor-associated and non-receptor-associated tyrosine kinases. Phospholipases of the D type, which hydrolyze phosphatidylcholine to phosphatidic acid, are regulated by members of the ADP-ribosylation factor and Rho subfamilies of small G proteins, and by protein kinase C and other factors. This review presents recent information concerning the molecular details of G protein regulation of these phospholipases.