Cells communicate through complex mechanisms that typically involve receptors and ligands that bind to them. Endogenous ligands have been identified for the vast majority of cellular receptors, helping explain receptor existence and function. But in the case of sigma-1 receptors, which interact with a diverse array of psychoactive drugs, an endogenous ligand has remained elusive. Now, researchers show that choline is an endogenous activator of sigma-1 receptors.