The origin and development of the Pichia pastoris expression system is described from its roots as an organism for the production of single-celled protein (SCP) to its evolution into a major host for the synthesis of recombinant proteins. Throughout its history, the ability of P. pastoris to grow on methanol as a sole source of carbon and energy to extremely high densities in fermenter cultures has been a central theme. The expression system would not be what it is today without the efforts of numerous talented researchers in fields from molecular biology to bioprocess engineering. As products made using P. pastoris take their places in world markets, it is clear that the future of the system is bright.