Prader-Willi Syndrome (PWS) is a non-inherited genetic condition that occurs spontaneously in 1 in 15 000 people worldwide. There are at least 1800 people with PWS in Australia. It is due to the loss of gene function of the paternal Chromosome 15 in the critical ‘Prader-Willi region’ of 15q11 – q13. Nearly every body system can be affected by PWS. The key features include hypotonia, feeding difficulties in infancy, followed by the onset of severe hyperphagia from around age 2-3 years. Hypogonadism is almost universal and most have growth hormone deficiency, manifesting with short stature, low muscle mass and small hands and feet. Hypothyroidism is common but central adrenal insufficiency is rare. Other features include mild to moderate intellectual disability with poor auditory processing, executive function and abstract thinking. Behavioural problems include emotional outbursts, body focused self-harm, repetitive and ritualistic behaviours, rigidity and perseveration. Abnormalities of mental health include situational anxiety (anxiousness), mood instability, affective disorder and, much less commonly, psychosis. Fortunately, there have been significant advances in understanding the genetics of PWS as well as the discovery of treatments that can markedly alter its trajectory. The focus of this talk will be to discuss the important endocrine disturbances that may occur in adults with PWS and the interventions that can change the course of the disease. Some of the newer and investigational therapies for people with PWS will also be highlighted.