A great challenge is the coupling of very sensitive microelectronic devices to wet biological systems in the generation of biomimetic sensors. Lipid membranes on solid supports (electrodes or semiconductors) may become the matrix of future bioelectronic devices probing and controlling biomolecular processes for scientific and technical applications. A sufficient electrical isolation between the coupling region and the surrounding electrolyte is mandatory. An attached lipid membrane with integral natural or designed proteins may be the material of choice if the biological components are kept in a proper environment. To retain the fluidity and stability of the lipid membrane and to provide an ion reservoir and space for bulky integral proteins, a separating layer composed of crystalline arrays of monomolecular proteinaceous subunits, termed S-layer, can be self-assembled on metal or semiconductor surfaces. In this way S-layer-supported lipid membranes are biomimetic structures mimicking the supramolecular principle of archeal cell envelopes. These composite architectures may ascend toward exciting new key devices, particularly in fields of membrane protein-based biosensors or lab-on-a-chip technology.