Community-based opioid overdose prevention programs (OOPPs) that include the distribution of naloxone have increased in response to alarmingly high overdose rates in recent years. This systematic review describes the current state of the literature on OOPPs, with particular focus on the effectiveness of these programs. We used systematic search criteria to identify relevant articles, which we abstracted and assigned a quality assessment score. Nineteen articles evaluating OOPPs met the search criteria for this systematic review. Principal findings included participant demographics, the number of naloxone administrations, percentage of survival in overdose victims receiving naloxone, post–naloxone administration outcome measures, OOPP characteristics, changes in knowledge pertaining to overdose responses, and barriers to naloxone administration during overdose responses. The current evidence from nonrandomized studies suggests that bystanders (mostly opioid users) can and will use naloxone to reverse opioid overdoses when properly trained, and that this training can be done successfully through OOPPs.