The preoperative period can be a traumatic time for young children undergoing surgery. Pediatric anesthesiologists strive to minimize distress for children in the operating room (OR) environment and to provide a smooth induction of anesthesia. Preoperative anxiety stimulates the sympathetic, parasympathetic, and endocrine systems, leading to an increase in heart rate (HR), blood pressure, and cardiac excitability. Various drugs have been advocated as premedication to allay anxiety and facilitate the smooth separation of children from parents. The ideal premedicant in children should be readily acceptable and should have a rapid and reliable onset with minimal side effects. Dexmedetomidine is a tasteless, colorless, and odorless drug that acts as a selective α-2 adrenergic agonist with both sedative and analgesic effects via actions in the central nervous system. Ketamine is an N-methyl-d-aspartate receptor antagonist that produces a state of sedation, anesthesia, immobility, analgesia, amnesia, and dissociation from the environment. Midazolam is a water-soluble benzodiazepine known to have a rapid onset and short duration of action, as well as properties of amnesia and anxiolysis. Administered intranasally, midazolam is an effective option for conscious sedation.