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Drug-involved offenders long have been over-represented in prisons. Intensified drug law enforcement in many countries strengthened the relationship between drug use and imprisonment, producing rising incarceration rates, especially for drug offenses, and rising numbers of drug-involved prisoners. Their growing number is attributable to four features of drugs and drug markets. Drug use disorders typically are not the only problems facing drug-involved prisoners. A high proportion exhibit severe mental health problems such as major depression, personality disorders, and psychotic disorders. Prior to incarceration, many drug-involved prisoners have unstable housing and are at high risk of homelessness; the risk of homelessness is increased by a term of incarceration. The high concentration of drug-involved offenders in prisons presents numerous problems for criminal justice authorities in prison and afterwards. Upon release, the most obvious challenges are high rates of drug relapse and recidivism. Formerly incarcerated individuals have extraordinarily high risk for drug overdoses shortly after release and, in the long-term, diseases acquired during imprisonment are transmitted in the community. The clustering of individuals in prison presents an opportunity to intervene; effective prison-based drug treatment holds the promise of breaking this cycle and mitigating the physical and mental health problems common among drug-involved prisoners.