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One approach to manage people with behaviours of concern including agitated or aggressive behaviours in health care settings is through the use of fast‐acting medication, called chemical restraint. Such management often needs to be delivered in crisis situations to patients who are at risk of harm to themselves or others. This paper summarizes the available evidence on the effectiveness and safety of chemical restraint from 21 randomized controlled trials (RCTs) involving 3788 patients. The RCTs were of moderate to high quality and were conducted in pre‐hospital, hospital emergency department, or ward settings. Drugs used in chemical restraint included olanzapine, haloperidol, droperidol, risperidol, flunitrazepam, midazolam, promethazine, ziprasidone, sodium valproate, or lorazepam. There was limited comparability between studies in drug choice, combination, dose, method of administration (oral, intramuscular, or intravenous drip), or timing of repeat administrations. There were 31 outcome measures, which were inconsistently reported. They included subjective measures of behaviours, direct measures of treatment effect (time to calm; time to sleep), indirect measures of agitation (staff or patient injuries, duration of agitative or aggressive episodes, subsequent violent episodes), and adverse events. The most common were time to calm and adverse events. There was little clarity about the superiority of any chemical method of managing behaviours of concern exhibited by patients in Emergency Departments or acute mental health settings. Not only is more targeted research essential, but best practice recommendations for such situations requires integrating expert input into the current evidence base. [ABSTRACT FROM AUTHOR]