Cholesteryl ester transfer protein (CETP) is important clinically and is the current target for new drug development. Its structure and mechanism of action has not been well understood. We have combined current new structural and functional methods to compare with relevant prior data. These analyses have led us to propose several steps in CETP's function at the molecular level, in the context of its interactions with lipoproteins, e.g., sensing, penetration, docking, selectivity, ternary complex formation, lipid transfer, and HDL dissociation. These new molecular insights improve our understanding of CETP's mechanisms of action.