1. T. Matthew Shields, MD* 2. Jenifer R. Lightdale, MD, MPH* 1. *Division of Pediatric Gastroenterology and Nutrition, UMass Memorial Children’s Medical Center, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA * Abbreviations: 5-HT: : 5-hydroxytryptamine CHS: : cannabinoid hyperemesis syndrome CTZ: : chemoreceptor trigger zone CVS: : cyclic vomiting syndrome EGD: : esophagogastroduodenoscopy FPIES: : food protein–induced enterocolitis syndrome GER: : gastroesophageal reflux GERD: : gastroesophageal reflux disease IEM: : inborn error of metabolism PS: : pyloric stenosis SMA: : superior mesenteric artery 1. There are at least 4 known physiologic pathways that can trigger vomiting, 3 of which are extraintestinal. 2. Understanding which pathway is causing a patient’s vomiting will help determine best treatment options, including which antiemetic is most likely to be helpful to mitigate symptoms. 3. Bilious emesis in a newborn should indicate bowel obstruction. 4. Cyclic episodes of vomiting may be indicative of a migraine variant. After completing this article, readers should be able to: 1. Understand the main pathways that trigger vomiting via the emetic reflex. 2. Differentiate among acute, chronic, and cyclic causes of vomiting. 3. Create a broad differential diagnosis for vomiting based on a patient’s history, physical examination findings, and age. 4. Recognize red flag signs and symptoms of vomiting that require emergent evaluation. 5. Recognize when to begin an antiemetic medication. 6. Select antiemetic medications according to the presumed underlying mechanism of vomiting. Vomiting is a common symptom of numerous underlying conditions for which children frequently present for healthcare. Although vomiting can originate from the gastrointestinal (GI) tract itself, it can also signal more generalized, systemic disorders. Vomiting in children is often benign and can be managed with supportive measures only. Still, clinicians must be able to recognize life-threatening causes of vomiting and to avoid serious associated complications, including electrolyte abnormalities, dehydration, or even bowel necrosis. Vomiting is defined as the forceful expulsion of gastric contents through the mouth and/or nose. Vomiting differs from gastroesophageal reflux (GER) and regurgitation in that the latter 2 conditions are characterized by effortless retrograde flow of duodenal or gastric …