Compared to the general population, higher levels of substance use are generally considered a normalised part of student life. This contribution adds to the limited body of knowledge on students’ substance use patterns in South African contexts, specifically insofar as alcohol, tobacco, cannabis, hard drugs and prescription medication are concerned. Voluntary selection techniques were followed to gather data by means of a self-administered survey from 818 students. The use of alcohol and prescription medication featured fairly prominently among students, followed by tobacco use. A marginal proportion of students engaged in the use of hard drugs, while cannabis use prevailed as a cause for concern. In line with local and international evidence, male students presented higher levels of alcohol, tobacco and cannabis use, while female respondents appear more prone to the use of prescription medication. Significant differences in students’ substance use mimic the South African realities of racial inequalities vis-à-vis socio-economic status, where White students, those from higher income groups and having attended a private school show elevated frequencies of substance use. While the General Strain Theory provides some insights into the dynamics of prescription substance use, social learning theories appear better suited to explain experimentation, socialisation and enculturation into substance use, especially so given the increase of substance use between academic year levels.