Lipids are metabolites with enormous structural and functional diversity. In biological systems, they function as sources of energy, form physical barriers, and orchestrate cellular signaling and trafficking in manifold ways. Because of the large number of lipids, complex metabolic networks, small size, and physicochemical properties, the elucidation of their biological functions has been challenging. I will present on chemical biology approaches that address some of these challenges by expanding our ability to control lipid function with high spatiotemporal precision, to target membrane proteins including Ras, Rho, and Rab GTPases, and to modulate protein-membrane interfaces with novel pharmacology.