The prevalence and costs of alcohol and drug disorders pose a serious social concern for policymakers. In this paper, we use data from the National Household Surveys on Drug Abuse (NHSDA) to estimate simple descriptive statistics and analysis of variance (ANOVA) models of the relationship between symptoms of dependence and labor market outcomes for alcohol, cigarettes, marijuana, and other illicit drugs. For men, we find that substance use with symptoms of dependence is associated with both lower employment rates and fewer hours of work. For women, we find that substance use with symptoms of dependence is associated with lower employment rates, but we find no consistent evidence of a relationship between symptoms of dependence and the number of hours worked. Finally, all of our point estimates are smaller in magnitude when we control for multiple substance use, suggesting that comorbidities play a critical role in the relationship between substance use and labor market outcomes. Our results suggest that policymakers and researchers should consider the full spectrum of substance use and dependence rather than focusing on the simple use of a single substance.