The current article summarizes the results of a comprehensive review of the international research published between 1990 and 2010. The research was focused on the prevalence of substance use/disorders among the unemployed and employed, the impact of substance abuse on unemployment and vice versa, the effect of unemployment on alcohol/ drug addiction treatment and smoking cessation, and the relationship between business cycle, unemployment rate and substance use. Over hundred-thirty relevant studies were identified investigating these issues. The main results are as follows: (1) Risky alcohol consumption (associated with hazardous, binge, and heavy drinking) is more prevalent among the unemployed. They are also more likely to be smokers, to use illicit and prescription drugs, and to have alcohol and drug disorders (abuse, dependence). (2) Problematic substance use increases the likelihood of unemployment and decreases the chance of finding and holding down a job. (3) Unemployment is a significant risk factor for substance use and the subsequent development of substance use disorders. However, the current research provides only limited information about which individuals are more likely to be affected. (4) Unemployment increases the risk of relapse after alcohol and drug addiction treatment. (5) The exact nature of the relationship between unemployment and the probability of smoking cessation remains unclear due to the mixed results observed in the literature review. (6) Drinking and smoking patterns appear to be procyclical. We see a decrease in both when the economy declines and the unemployment rate increases. In contrast, a countercyclical trend was observed amongst adolescent drug users. However, these studies do not provide any convincing or additional information about substance use amongst the unemployed. This paper discusses the merits, limitations and problems of the research, proposes numerous future research questions, and outlines important implications for policy makers and practitioners, especially with regard to prevention and vocational promotion and rehabilitation.