Solid/gas biocatalysis is a nontraditional reaction system that employs the ability of some enzymes, being in the solid state, to catalyze reactions of substrates in the gas phase. Manipulation of the reaction parameters (temperature and pressure) in the solid/gas system allows precise control over the thermodynamic activity of water and substrate and creation of a controlled microenvironment for the enzyme, making it an appropriate model for enzymology studies. Owing to such advantages as high stability of dry enzymes and cofactors and easy fractionation of gas mixtures, solid/gas biotechnology has already found several industrial applications. Here we review key thermodynamic factors affecting the properties of enzymes, including their activity and stability, in a solid/gas system. Examples of promising enzymes and microorganisms for development and improvement of solid/gas biocatalytic technologies in organic synthesis, biosensors, and green chemistry are discussed.