Adolescence is a time of physical and mental development when small changes can impact on the rest of a person's life. Substance use in this crucial period can have long-lasting consequences for the individual and for society. The prevalence of substance use in young people is an area of concern for policy makers and health workers. This systematic review looked at prevalence for four substances: alcohol, tobacco, cannabis, and benzodiazepines, across the Republic of Ireland for persons between the ages of 13 and 24, and compared usage between 2000 and 2012. Eighteen articles were included in the review. It was seen that tobacco, alcohol, and cannabis use has fallen in the lifetime and previous month use. The level of benzodiazepine use has remained similar in the period of study. Future work should redress the imbalance in substance use research that sees the majority of researchers looking at a few substances while little work is done on the others.