This study investigated gender differences in the relationship between psychoactive substance use and sexual thoughts, feelings, and behaviors. Participants (N = 464) were male and female alcohol, opiate, cocaine, and methamphetamine users enrolled in an outpatient treatment program at any of 8 sites. A self-report survey that inquired about the specific sexual thoughts, feelings, and behaviors of the participant during previous instances of being under the influence of their primary drug of dependence served as the data source. The results indicate that different categories of psychoactive agents were associated with different effects on sexual behavior, and that those effects vary by gender. Development of a valid measure assessing the type and strength of these relationships may be beneficial for use by treatment programs in promoting abstinence from drug and alcohol use and preventing relapse.