Pulmonary aspiration, defined as the inhalation of oropharyngeal or gastric contents into the larynx and lower respiratory tract, is arguably the most feared and potentially life-threatening sedation-related adverse event. Patients with a “full stomach” are thought to be at risk of aspirating when deeply sedated as the competence of the lower esophageal sphincter and airway protective reflexes are diminished or absent under these conditions. Historically, the risk of aspiration was thought to be directly related to the duration of fasting from solids and liquids. However, our understanding has evolved over the last several decades; we now know other factors such as patient age, presence of comorbidities, procedure type, and sedation depth and duration also influence aspiration risk. We have also come to understand that fasting prior to procedures has unintended negative effects in some groups of children. A more nuanced approach to fasting prior to sedation has been developed by several specialty societies and organizations to account for advances in knowledge of aspiration. Strategies for assessing and mitigating patient risk are also discussed.