Early diagnosis of phenylketonuria (PKU) became a goal worth pursuing following demonstration of the efficacy of the dietary treatment conceived by Louis I Woolf. This paper narrates the history of this treatment, describes Woolf's role in the establishment of neonatal PKU screening and surveys his other contributions to our understanding of this condition. If Woolf, Centerwall, Baird and Berry had waited until all the scientific evidence about PKU that is now at our disposal had been brought to light, there would still be no neonatal screening programmes.