This study investigated the impact of drug use on employment over 20 years among men and women, utilizing data on 7,661 participants in the National Longitudinal Survey of Youth. Growth mixture modeling was applied, and five distinct employment trajectory groups were identified for both men and women. The identified patterns were largely similar for men and women except that a U-shape employment trajectory was uniquely identified for women. Early-initiation drug users, users of "hard" drugs, and frequent drug users were more likely to demonstrate consistently low levels of employment, and the negative relationship between drug use and employment was more apparent among men than women. Also, positive associations between employment and marriage became more salient for men over time, as did negative associations between employment and childrearing among women. Processes are dynamic and complex, suggesting that throughout the life course, protective factors that reduce the risk of employment problems emerge and change, as do critical periods for maximizing the impact of drug prevention and intervention efforts.