Prisons inmates have high rates of substance abuse and associated social and health problems, and a concomitant high need for drug treatment while incarcerated. Female inmates have an even greater treatment need, yet most inmates do not participate in treatment while incarcerated. Using data from a nationally representative sample of prison inmates, this article examines the impact of gender on prison treatment participation and gender differences in the factors associated with clinical treatment participation. Females were significantly more likely to participate in prison drug treatment than males, controlling for other factors. For both males and females, severity of drug problems predicted participation in treatment. For males but not females, race was associated with prison treatment participation, and among those with drug abuse or dependence, females with co-occurring mental health problems were more likely to participate in treatment. Implications for prison assessment and treatment policies, and future research, are discussed.