The relationship between man and substances that have abuse potentials, and whose use has been associated with the development or progression of substance use disorders has continued to evolve in terms of geography, economic implications, and time. History shows that local plants with psychoactive constituents can get exported worldwide through global travel, commerce, or even conquest. Time and globalization also change people's relationship with substances of abuse; hence, an area that was initially alien to certain substances might evolve to becoming a trafficking hub, and then a destination. A case in point is Africa where a rapidly increasing prevalence of substance use/abuse and substance use disorder among adolescents and young adults is putting enormous strain on the economy, healthcare system, and society at large. However, there appears to be a paucity of scientific literature and data on the epidemiology, risk assessment, and contributing factors to substance use and the development of substance use disorders across Africa. In this narrative review, we examine extant literature (PubMed, Google scholar, Medline) for information on the prevalence, trends, and influencers of substance use and the development of substance use disorders. This is with a view of understanding the determinants of substance use and factors that influence the development of substance use disorders in the region, and how this information can be channeled towards developing a comprehensive intervention and treatment program.