Nausea and vomiting are symptoms resulting from a triggered emetic reflex. Many endogenous and exogenous triggering factors can activate the emetic reflex, making understanding difficult and therapy challenging. The key to managing most cases of nausea and vomiting lies in a good history and a detailed physical examination. Most episodes of acute vomiting (lasting < 48 hours) have an evident triggering factor (eg, infection, viral illness, or food poisoning) and can be managed by removing the triggering agent and via supportive therapy. Chronic and unexplained nausea and vomiting can be a challenge. The cause is often obscure and requires special investigation. Functional gastroduodenal disorders such as cyclic vomiting syndrome, functional vomiting, and chronic idiopathic nausea should be considered if investigations are unrevealing. Knowledge regarding various emetic pathways and the specific neurotransmitters involved helps to target therapy. Histamine-1 receptor antagonists and muscarinic antagonists are suitable candidates for motion sickness and labyrinthine disorders. Phenothiazines, 5-hydroxytryptamine-3 receptor antagonists, corticosteroids, and benzodiazepines have a role in postchemotherapy and postoperative nausea and vomiting. Cannabinoid and neurokinin-1 receptor antagonists are best reserved for refractory cases of nausea and vomiting. Motilin agonists and metoclopramide are useful for treating impaired gastric motility disorders.