Abstract The current interest in reconstituting biological membranes on solid supports aims at linking the biological world, with its elaborate molecular architectures, properties, and functions, to the field of surface science, with its advanced technologies and sophisticated surface-sensitive analytical methods. Success in this enterprise would not only improve our understanding and description of basic cellular functions but also help developing biotechnological tools, biomedical devices, or biofunctional materials. To achieve this goal, reliable methods need to be developed for controlling the formation of solid-supported lipid membranes and the deposition, incorporation, and addressing of biological entities, from molecules to cells. This review focuses on a versatile approach that combines the formation of solid-supported lipid bilayers (SLBs) by deposition of lipid vesicles with the adsorption of proteins and formation of ordered protein layers via specific interaction with ligands incorporated in the SLBs. This approach provides access to basic aspects of membrane biophysics, membrane-protein interactions, and molecular ordering in two dimensions. It may also constitute a strategy for the design of biofunctional surfaces at the nanoscale.