In this clinical article, Dr. James C Harris, Director of Developmental Neuropsychiatry in the Departments of Psychiatry and Pediatrics at the Johns Hopkins University School of Medicine reviews Lesch-Nyhan disease, a metabolic disorder resulting from hypoxanthine phosphoribosyltransferase 1 deficiency. This X-linked genetic disorder is characterized by hyperuricemia, intellectual disability, early hypotonia with onset of a predominantly dystonic movement disorder by 6 months, subsequent dysarthric speech, and compulsive self-injury with self-mutilation along with an extended cognitive/behavioral phenotype. Studies in an Hprt1-deficient mutant mouse model and PET imaging studies have documented dopaminergic dysfunction with basal ganglia involvement. Management of hyperuricemia with allopurinol, dental management, orthopedic management, and use of protective equipment, along with behavioral interventions, is mandatory. Pharmacology targets stabilization of mood and anxiety management. Three cases have been treated with deep brain stimulation with reduction of self-injury and some modification of dystonia.