Many adult patients with phenylketonuria (PKU) are no longer receiving treatment for their disorder despite mounting evidence that elevated blood phenylalanine levels are associated with impairments of brain function manifested by neurocognitive deficits and psychiatric symptoms. An outreach program was established in a single PKU clinic with the goal of bringing "wayward" adults back into treatment. In a clinic with 152 active patients, another 162 records were identified of patients who had been previously treated and had not transferred to another clinic. 47 of these patients could not be located. Of the remaining 115, a total of 63 were re-engaged and received education, either through individual telephone encounters or attendance at adult educational programs. Thus far, 21 patients have returned to treatment. Obstacles to treatment for many patients include inadequate insurance coverage and lack of understanding of the significance of the diagnosis of PKU among patients off treatment for many years. The social, emotional and psychiatric symptoms of the disorder itself are perhaps the greatest barrier to successful re-introduction to treatment. This experience confirms that there are large numbers of adult patients with PKU who are not currently receiving any care for their disorder. Reaching them and re-engaging them in treatment will be a significant challenge and will require a multifaceted effort.