The growing use of Air-Lift Reactors (ALR) in biotechnology can be attributed to their simple design, high rates of mass transfer and efficient mixing in the liquid phase, and the possibility of culturing shear sensitive cells and enzymes immobilized within low density particles. This paper reviews ALR design and operation, and some representative examples of their application, based on the research and development carried out over the last ten years at the University of Belgrade. Fluid-dynamic, mixing, mass transfer and kinetic studies resulted in mathematical models that can be used in reactor design and process scale up. The ALR prototypes equipped with process control hardware were specifically designed for lipase catalyzed oil interesterification, beer fermentation, production of monoclonal antibodies in mammalian cell culture, and production of anthraquinons in plant cell culture.