Sphingolipids and their metabolites play key cellular roles both as structural components of membranes and as signaling molecules that mediate responses to physiologic cues and stresses. Despite progress during the last two decades in defining the enzymatic machinery responsible for synthesizing and degrading sphingolipids, comparatively little is known about how these enzymes are regulated to ensure sphingolipid homeostasis. Here, we review new insights into how cells sense and control sphingolipid biosynthesis and transport. We also discuss emerging evidence that sphingolipid metabolism is closely coordinated with that of sterols and glycerolipids and with other processes that occur in the secretory pathway. An improved understanding of sphingolipid homeostasis promises to shed light on basic processes in cell biology and disease, including how cells establish and maintain the complex membrane composition and architecture that is a defining feature of eukaryotic cell biology.