The thin membrane of the endoplasmic reticulum matures into the thick plasma membrane in the Golgi apparatus. Along the way, the concentrations of cholesterol and sphingolipids increase. Here, Gerrit van Meer discusses how this phenomenon may reflect an intricate lipid-protein sorting machinery. Synthesis of sphingolipids, translocation across the Golgi membrane and lateral segregation into lumenal domains seem to be key events. In addition, signalling lipids indicate the lipid status of the Golgi and interact with proteins of the transport machinery to regulate membrane flux.