Background Social connections can lead to contagion of healthy behaviors. Successful treatment of patients with opioid use disorder, as well as recovery of their communities from the opioid epidemic, may lay in rebuilding social networks. Strong social networks of support can reinforce the benefits of medication treatments that are the current standard of care and the most effective tool physicians have to fight the opioid epidemic.Methods We conducted a systematic review of electronic research databases, specialist journals and grey literature up to August 2020 to identify experimental and observational studies of social network support in patient populations receiving medication for opioid use disorder (MOUD). We place the studies into a conceptual framework of dynamic social networks, examining the role of networks before MOUD treatment is initiated, during the treatment, and in the long-term following the treatment. We analyze the results across three sources of social network support: partner relationships, family, and peer networks. We also consider the impact of negative social connections.Results Of 5193 articles screened, 46 studies were identified as meeting inclusion criteria (12 were experimental and 34 were observational). 39 studies indicated that social network support, or lack thereof, had a statistically significant relationship with improved MOUD treatment outcomes. We find the strongest support for the positive impact of family and partner relationships when integrated into treatment attempts. We also identify strong evidence for a negative impact of maintaining contacts with the drug-using network on treatment outcomes.Conclusions Social networks significantly shape effectiveness of opioid use disorder treatments. While negative social ties reinforce addiction, positive social support networks can amplify the benefits of medication treatments. Targeted interventions to reconstruct social networks can be designed as a part of medication treatment with their effects evaluated in improving patients’ odds of recovery from opioid use disorder and reversing the rising trend in opioid deaths.