Membrane lipids function as structural molecules, reservoirs for second messengers, membrane platforms that scaffold protein assembly and regulators of enzymes and ion channels. Such diverse lipid functions contribute substantially to cellular mechanisms for fine-tuning membrane-signaling events. Meaningful coordination of these events requires exquisite spatial and temporal control of lipid metabolism and organization, and reliable mechanisms for specifically coupling these parameters to dedicated physiological processes. Recent studies suggest such integration is linked to the action of phosphatidylinositol transfer proteins that operate at the interface of the metabolism, trafficking and organization of specific lipids.