A survey is given on “top-down” and “bottom-up” approaches to the design of nanostructured sensors which monitor different physical and chemical quantities. Particular emphasis is put on new materials and transducers for molecular recognition by chemical sensors. They convert chemical information into electronic signals by making use of suitable “key-lock” structures. This requires the control of atomic structures of chemically sensitive materials under either thermodynamically or kinetically controlled conditions. This in turn requires the molecular understanding of sensor mechanisms which is deduced from comparative microscopic, spectroscopic, and sensor test studies on “prototype materials”. Selected examples illustrate typical mechanisms of molecular recognition with electron conductors, ion conductors, mixed conductors, molecular cages, polymers, and biomolecular function units.