Gastroschisis is an abdominal wall defect typically located to the right of the umbilical cord in which intestines and occasionally other abdominal contents herniate through the abdominal wall opening. The etiology of this defect is unknown. The increased recurrence risks observed in families with a child with gastroschisis suggest that genetic factors play a role in its causation. However, non-genetic factors are also important, as evidenced by the increased occurrence of gastroschisis among younger mothers, the increasing prevalence of gastroschisis in recent years observed by several birth defects surveillance systems, and the frequent occurrence of gastroschisis in a cluster pattern. Despite recognition of the importance of non-genetic factors in gastroschisis causation, no factors, other than young maternal age, have been definitively identified, limiting the development of prevention strategies. This article summarizes the currently available literature on non-genetic risk factors for gastroschisis, including investigations of sociodemographic factors, maternal therapeutic medication and non-therapeutic drug exposures, chemical exposures, and other factors. The article also discusses some of the challenges faced by investigators working to better understand gastroschisis etiology. Published 2008 Wiley-Liss, Inc.