There is evidence and consensus that early strict control of blood PHE is associated with higher IQ, and that high blood PHE concentrations throughout lifetime has a negative impact on measures of executive function as well as psychiatric and neurological well-being. Evaluating the evidence to determine the optimal blood PHE treatment range for individuals with PKU is confounded by factors that impact blood PHE at the time of NBS and/or diagnosis (age, diet and health status when determined, differences in methodology); as well as by genotype, nutritional status, treatment history during critical periods of development, and variability of blood PHE. In addition, it is difficult to compare studies that use lifetime blood PHE with those that use concurrent blood PHE. Nevertheless, while recognizing that there are individuals who appear to do well with blood PHE concentrations between 360 and 600 µmol/L, and that adolescents and adults often find it difficult to maintain blood PHE within the treatment range, current evidence supports the recommendation that treatment should be initiated in all individuals with a blood PHE >360 µmol/L and a lifetime blood PHE of 120-360 µmol/L should be maintained.