Furin is a secretory pathway endoprotease that catalyses the maturation of a strikingly diverse group of proprotein substrates, ranging from growth factors and receptors to pathogen proteins, in multiple compartments within the trans-Golgi network (TGN)/endosomal system. This review focuses on recent developments in the biochemistry and cell biology of the endoprotease, including the mechanism of TGN localization, phosphorylation-dependent regulation of protein traffic, and novel insights into early embryogenesis, extracellular matrix formation and pathogen virulence.