HIV/AIDS is one of the leading causes of death among reproductive-age women throughout the world, and substance abuse plays a major role in HIV infection. We conducted a systematic review, in accordance with the 2015 Preferred Items for Reporting Systematic Reviews and Meta-analysis tool, to assess HIV risk-reduction intervention studies among reproductive-age women who abuse substances. We initially identified 6,506 articles during our search and, after screening titles and abstracts, examining articles in greater detail, and finally excluding those rated methodologically weak, a total of 10 studies were included in this review. Studies that incorporated behavioral skills training into the intervention and were based on theoretical model(s) were the most effective in general at decreasing sex and drug risk behaviors. Additional HIV risk-reduction intervention research with improved methodological designs is warranted to determine the most efficacious HIV risk-reduction intervention for reproductive-age women who abuse substances.