The administration of oral sedatives for minimal and moderate sedation is common practice for pediatric dentistry. Being up to date with contemporary medications and dosing recommendations is imperative for patient safety. Historic medications such as chloral hydrate have become obsolete with the introduction of benzodiazepines and other newer medications such as alpha-2 adrenergic agonists. Oral opioids are useful for analgesia and mild sedation but may result in significant respiratory depression when combined with other central nervous system depressants and, if left untreated, hypoxemia. Antihistamines can provide minimal sedation but may have other added benefits such as antiemetic and antisialagogue effects. This review will discuss relevant pharmacologic aspects, including onset, duration of action, metabolism, and adverse reactions, for several common agents used for minimal and moderate oral sedation to assist practitioners in determining ideal medications or combinations that fit the needs of the pediatric patient and dental procedure contingent upon the provider’s level of training.