The mortality risk for recently released prisoners is alarmingly high. These individuals, especially in the first 2 weeks following release, are at an increased risk for death compared with an age- and gender-matched general population, with the majority of fatalities attributed to overdoses. Although a number of factors contribute to these incidents, the decreased tolerance resulting from a period of abstinence during incarceration is believed to be especially important. Other important factors are the concurrent use of multiple drugs, the lack of pre-release counseling and post-release follow-up, and the failure to identify those at greatest risk. This chapter describes studies conducted in various countries on post-release drug-related deaths. The literature review supports the finding that there is a significantly heightened risk of overdose death during the initial post-release period and suggests a number of prevention and harm reduction responses that may be applied at various levels of the criminal justice system to reduce drug-related deaths in ex-prisoners. Some identified potential preventive responses are the provision of opioid substitution therapy delivered in combination with psychosocial intervention for opioid-dependent prisoners and a continuity of care and stability of treatment through all stages of the criminal justice system, including during community integration, which can be supported by close linkages between prison-health and public-health systems. Take-home naloxone programs are another promising strategy to prevent overdose deaths among people recently released from prison.