Results of this review reveal compelling evidence for both substitution and complementary effects, suggesting nuanced yet significant distinctions across different populations examined in these studies. Several mechanisms for the impact of cannabis use on alcohol-related outcomes are identified, including patterns and context of co-use, timing and order of use, cannabinoid formulation, pharmacokinetic interactions, and user characteristics (including diagnostic status), all of which may influence substitution versus complementary effects. This review will inform future research studies examining this topic in both clinical and community samples and aid in the development of treatment and prevention efforts targeting those populations most vulnerable to negative consequences of co-use. Finally, this review highlights the need for additional research in more diverse samples and the use of mixed-methods designs to examine both pharmacological and contextual influences on co-use.