The use of inhalational anesthetics was first publicly demonstrated in 1846. Alcohol has been consumed for centuries and is now our most costly drug abuse problem. Despite widespread use, the molecular mechanism of action of these drugs has remained an enigma. The prevailing theory suggests that alcohol and anesthetics interact directly with neuronal membrane proteins to cause their effects. Our laboratories are using a variety of cutting edge approaches to gain insight into the mechanism of action of these drugs. Biophysical approaches such as high-resolution nuclear magnetic resonance (NMR) spectroscopy and genetic engineering approaches such as creation of designer mice are currently being used by our laboratories. These approaches are providing exciting insight into how these drugs exert their effects. This research could ultimately result in safer and better anesthetics, may lead to treatments for alcoholism, and may provide insight into basic biologic processes such as consciousness.