The assessment of pre-procedure fasting and control of sedation depth are prominent elements of widely disseminated procedural sedation guidelines and of the Joint Commission on Accreditation of Healthcare Organizations' standards. Both exist primarily to minimize the risk of pulmonary aspiration of gastric contents. This paper critically examines the literature on pre-procedure fasting and controlling sedation depth in association with pulmonary aspiration, and interprets this evidence in the context of modern emergency medicine practice. The article reviews the pathophysiology of aspiration and changing concepts regarding aspiration risk over the last decade. After reviewing studies on aspiration risk during general anesthesia, the paper reviews the risk of aspiration during labor and delivery as a more appropriate comparison group for aspiration risk during emergency department procedural sedation and analgesia (ED PSA). It is noted that aspiration during ED PSA has not been reported in the medical literature and that aspiration during general anesthesia and labor and delivery is uncommon. The literature provides no compelling evidence to support specific fasting periods for either liquids or solids prior to PSA, and existing guidelines for elective patients are of necessity arbitrary and based upon consensus opinion. The article discusses the implications in the areas of training and preparedness, monitoring, and research for the emergency physician practicing PSA.