Discovered in 1981 by Tanaka and Murao (Agric Biol Chem 45:2383-2384, 1981), bilirubin oxidase (BOD) is a sub-group of multicopper oxidases (MCOs) also utilizing four Cu+/2+ ions. It catalyzes the oxidation of bilirubin to biliverdin, hence the classification of bilirubin oxidase, and has been primarily used in the determination of bilirubin in serum and thereby in the diagnostic of jaundice. Unlike laccases, the most studied MCOs, BODs display a high activity and stability at neutral pH, a high tolerance towards chloride anions and other chelators, and for some species, a high thermal tolerance. Therefore, BODs could potentially be an alternative to laccase which are so far mainly restricted to applications in acid media. Because of growing interest in BODs for numerous applications under mild pH conditions, based on the number of patents and publications published in the last 5 years, here I will summarize the available data on the biochemical properties of BODs, their occurrence, and their possible biotechnological use in (1) the field of Healthcare for the elaboration of biofuel cells or bilirubin sensors or (2) the field of environmentally desirable applications such as depollution, decolorization of dyes, and pulp bleaching.