Cell membranes are complex assemblies of lipids and proteins, stabilized by non-covalent interactions such as the hydrophobic effect and van der Waals forces. The two-molecule-thick fluid lipid bilayer provides the architectural matrix of the cell membrane and the non-polar environment in which membrane proteins, one of the most important and least studied biological macromolecules, reside as stable folded structures. In our research, we use diverse characterization techniques such as X-ray and neutron diffraction, fluorescence spectroscopy, circular dichroism spectroscopy, molecular modeling, etc., to uncover the structural and thermodynamic determinants of cell membrane assembly. In my talk, I will present results that provide the framework for understanding membrane protein structure, stability and interactions.