Administration of midazolam by nose or the buccal route (absorption via the gums and cheek) as an alternative to rectally administered diazepam is becoming increasingly popular for the emergency treatment of seizures in children. Midazolam is also used for endoscopyprocedural sedation and sedation in intensive care. The anterograde amnesia property of midazolam is useful for premedication before surgery to inhibit unpleasant memories. Midazolam, like many other benzodiazepines, has a rapid onset of action, high effectiveness and low toxicity level. Drawbacks of midazolam include drug interactions, tolerance, withdrawal syndrome as well as adverse events including cognitive impairment and sedation.Paradoxical effects occasionally occur and are most common in children, the elderly, and particularly after intravenous administration.

Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for preoperative sedation, for the induction of general anesthesia, and for sedation of ventilated patients in critical care units.^[13][14] Midazolam is superior to diazepam in impairing memory of endoscopy procedures, but propofol has a quicker recovery time and a better memory-impairing effect.^[12] It is the most popular benzodiazepine in the intensive care unit (ICU) because of its short elimination half-life, combined with its water solubility and its suitability for continuous infusion. However, for long-term sedation, lorazepam is preferred due to its long duration of action,^[17] and propofol has advantages over midazolam when used in the ICU for sedation, such as shorter weaning time and earlier tracheal extubation.^[18] There is evidence buccal and intranasal midazolam is easier to administer and more effective than rectally administered diazepam in the emergency control of seizures.^[19][20][21] In the final stages of end-of-life care, midazolam is routinely used at low doses via subcutaneous injection to alleviate agitation, myoclonus, restlessness or anxiety in the last hours or days of life.^[22] At higher doses during the last weeks of life, midazolam is considered a first line agent in palliative continuous deep sedation therapy when it is necessary to alleviate intolerable suffering not responsive to other treatments,^[23] but the need for this is rare.^[24] Midazolam is also sometimes used in neonates who are receiving mechanical ventilation, although morphine is preferred, owing to its better safety profile for this indication.^[25]

Oral midazolam is indicated for the short-term treatment of moderately severe insomnia in patients who have not reacted adequately to other hypnotics, and who have persistent trouble in falling asleep. Because of midazolam's extremely short duration, it is not used for patients who have trouble staying asleep through the night; moderate- to long-acting benzodiazepines, such as temazepam, nitrazepam, flunitrazepam and lormetazepam, are used for those purposes. Like other benzodiazepines, midazolam produces a decrease in delta activity, though the effect of benzodiazepines on delta may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep; it is thought to reflect sleep quality, with lower levels of delta sleep reflecting poorer sleep. Thus, midazolam and other benzodiazepines cause a deterioration in sleep quality. Cyproheptadine may be superior to nitrazepam in the treatment of insomnia, as it enhances sleep quality based on EEG studies.^[26]

Midazolam in combination with an antipsychotic drug is indicated for the acute management of schizophrenia when it is associated with aggressive or out of control behaviour.^[27] It is also sometimes used for the acute management of seizures such as status epilepticus. Long-term use for the management of epilepsy is not recommended, however, due to the significant risk of tolerance (which renders midazolam and other benzodiazepines ineffective) and the significant side effect of sedation.^[28] A benefit of midazolam is that in children it can be administered buccally or intranasally at home or at school for emergency control of acute seizures, including status epilepticus.^[11][29] Midazolam is effective for refractory status epilepticus, and has advantages of being water-soluble, having a rapid onset of action and not causing metabolic acidosis from the propylene glycol vehicle, which occurs with other benzodiazepines. Drawbacks include a high degree of breakthrough seizures—due to the short half-life of midazolam—in over 50% of people treated, as well as treatment failure in 14–18% of people with refractory status epilepticus. Tolerance develops rapidly to the anticonvulsant effect, and the dose may need to be increased by several times to maintain anticonvulsant therapeutic effects. With prolonged use, tolerance and tachyphylaxis can occur and the elimination half-life may increase, up to days.^[15][30]