Opioid overdose can induce acute respiratory and central nervous system depression that may lead to death. Recently the numbers of opioid-related deaths or hospitalizations have increased in Canada and there is an ongoing opioid crisis. There were 3,023 and 4,588 apparent opioid-related deaths that occurred in 2016 and 2018 respectively. The rate of apparent opioid-related deaths was 7.9 per 100,000 population in 2016 nationally. This rate can be as high as 20.7 deaths and 14.4 deaths per 100,000 population in British Columbia and Alberta respectively in 2016. Synthetic opioids that are extremely potent, such as fentanyl, are used more prevalently than non-synthetic opioids. Naloxone, a medication that temporarily blocks the effects of opioids, has been advocated for a wider use in the communities. Naloxone works by competing for opioid receptors with opioids and remains active in the body for 20 to 90 minutes, shorter than most opioids. Without opioids, naloxone has little pharmacologic activity. Data from non-comparative studies suggest that naloxone use in a home or community setting for opioid overdose is associated with a low mortality rate. In Canada, take-home naloxone kits are available at most pharmacies without a prescription and are free in some provinces. A 2018 CADTH Environment Scan report identified that there are two to three doses of 0.4 mg or 1 mg naloxone in the naloxone kits in Canadian provinces. The formulations of naloxone available in the kits include naloxone nasal spray in Ontario or naloxone intramuscular injection in other provinces. Both take less than five minutes to take effect. In a 2017 CADTH report that evaluated different formulations of naloxone available in take-home naloxone kits, two randomized controlled trials (RCTs) were identified and compared intramuscular naloxone with naloxone administered intranasally using an atomization device. Higher proportions of patients receiving intramuscular naloxone achieved adequate response than those receiving intranasal naloxone. However, comparative evidence to support the use of take-home naloxone kits in pre-hospital settings may be limited. A 2014 CADTH Rapid Response report did not identify any primary studies or reviews on the effectiveness of naloxone administration in a home or community setting compared with naloxone use by health professionals. Since the release of the 2014 CADTH report, the use of naloxone in home and community settings has been evaluated in several studies or reviewed because of the ongoing opioid crisis and the potential benefits of naloxone use in such settings. This report aims to update the previous CADTH review on the clinical effectiveness and cost-effectiveness of the administration of naloxone in a home or community setting, as well as to identify evidence-based guidelines for its use.