Hallermann-Streiff syndrome is a rare congenital syndrome that is well-known but whose genetic cause has so far not been unraveled – although researchers have intensively investigated the disorder, using the latest applications of high-throughput sequencing, which have considerably facilitated the identification of disease-associated genes in recent years. Clinically, it presents as a combination of craniofacial dysmorphism, eye malformations, hair and skin anomalies, short stature, and, especially, a characteristic face that usually leads to the clinical diagnosis. Interestingly, affected children may also show signs of accelerated aging. Hallermann-Streiff syndrome thus belongs to the group of so called progeroid syndromes. In a review article published in the American Journal of Medical Genetics, researchers of the Institute of Human Genetics Göttingen summarize the current knowledge on the clinical characteristics of the syndrome and discuss the missing molecular link. Furthermore, they present innovative strategies that may be applied to identify the genetic basis of Hallermann-Streiff syndrome in the future.