Prader-Willi syndrome (PWS) is one of the most common genetic obesity syndrome. It is a genomic imprinting disorder, caused by loss of function of paternally expressed 15q11.2-q13 genes (PWS region), either due to a paternal deletion, maternal uniparental disomy (mUPD) of chromosome 15, or an imprinting defect causing silencing of the paternal alleles. This results in a well-known, but heterogeneous, clinical phenotype characterized by distinct dysmorphic features, muscular hypotonia and neonatal feeding difficulties often requiring nasal tube feeding in early life. From around the age of 2 onwards, patients often present with hyperphagia, which can result in obesity, neurobehavioral problems, and mild to moderate cognitive impairement. Furthermore, hypothalamic dysregulation can result in endocrine deficits, such as growth hormone deficiency, hypothyroidism, hypogonadism, and adrenal insufficiency. Other frequent symptoms include temperature dysregulation, ear infections, dental problems, gastro-intestinal complaints, scoliosis and strabismus. In clinical care, a multidisciplinaire approach is essential, involving several subspecialists, with particular focus on supporting a healthy and structured lifestyle. Growth hormone suppletion is advised, in particular because of beneficial metabolic effects, and substitution of other hormones is prescribed on indication.