Sphingolipids are ubiquitous components of eukaryotic cell membranes, where they play important roles in intracellular signaling and in membrane structure. Even though the biochemical pathway of sphingolipid synthesis and its compartmentalization between the endoplasmic reticulum and Golgi apparatus have been known for many years, the molecular identity of the enzymes in this pathway has only recently been elucidated. Here, we summarize progress in the identification and characterization of the enzymes, the transport of ceramide from the endoplasmic reticulum to the Golgi apparatus, and discuss how regulating the synthesis of sphingolipids might impact upon their functions.