ABSTRACT Background Self-Esteem (SE) may be a reason why students use substances. A dysfunctional family may be an issue that leads students to use drugs. There has been limited research on how drug use (DU) is a consequence of family dysfunction. Aims This study examines the associations between SE and DU and the moderating effects of dimensions of family dysfunction (problem-solving, communications, roles, affective response, affective involvement, behavior control, and general functioning) on this association. Methods 450 students completed the Psychoactive Substance Use Questionnaire, Family Assessment Device, and Index of Self-Esteem. Results The results indicated that roles significantly moderated the association between self-esteem and drug use, while the moderation effects of all other family dysfunction dimensions were insignificant. Conclusions The association between self-esteem and drug use and how roles moderate this association emphasize the need to create awareness in families and schools where these students can easily understand the consequences of their behavior.