The β-propeller fold appears as a very fascinating architecture based on four-stranded antiparallel and twisted β-sheets, radially arranged around a central tunnel. Similar to the α / β-barrel (TIM-barrel) fold, the β-propeller has a wide range of different functions, and is gaining substantial attention. Some proteins containing β-propeller domains have been implicated in the pathogenesis of a variety of diseases such as cancer, Alzheimer, Huntington, arthritis, familial hypercholesterolemia, retinitis pigmentosa, osteogenesis, hypertension, and microbial and viral infections. This article reviews some aspects of 3D structure, amino acids sequence regularities, and biological functions of the proteins containing β-propeller domains. Major emphasis has been laid on β-propellers whose functions are associated to human diseases. Recent research efforts reported in the fields of protein engineering, drug design, and protein structure-function relationship studies, concerning the β-propeller architecture, have also been discussed.