The yeast Saccharomyces cerevisiae is a model eukaryotic organism for the study of the regulation of phospholipid synthesis. The major phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine) are synthesized by complementary (CDP-diacylglycerol and Kennedy) pathways. The regulation of these pathways is complex and is controlled by genetic and biochemical mechanisms. Inositol plays a major role in the regulation of phospholipid synthesis. Inositol-mediated regulation involves the expression of genes and the modulation of enzyme activities. Phosphorylation is a major mechanism by which enzymes and transcription factors are regulated, and indeed, key phospholipid biosynthetic enzymes have been identified as targets of phosphorylation. Protein kinase A phosphorylates CTP synthetase, choline kinase, Mg2+-dependent phosphatidate phosphatase, phosphatidylserine synthase, and the transcription factor Opi1p. CTP synthetase and Opi1p are also phosphorylated by protein kinase C. The phosphorylation of these proteins plays a role in regulating their activities and (or) function in phospholipid synthesis.