The role of psychoactive substance use in the research of artistic creation and creativity is a long-standing topic. Ever since the discovery of LSD, researchers have examined the relationship between the effects of chemical substances and the artistic creative process. The goal of the present study was to systematically review all published empirical publications and case reports in refereed journals that focused on the relationship between psychoactive substances and creativity/creative artistic process. A total of 19 studies were identified that met the inclusion and exclusion criteria. Results were difficult to summarize because of the different study questions asked, the diverse methods used, the different samples applied, and the various substances examined. The general results suggest that there is an association between creativity and substance use. However, the studies were unable to show that substance use directly contributed to the growth of creativity or facilitated creative artistic process. It is concluded that specific skills may be subject to change as a consequence of substance use, and consequently may have an effect on the style of creation.