This article examines the role of Ecstasy (MDMA or 3, 4-methylenedioxymethamphetamine) as a drug used for self-medication and coping with both short- and long-term negative life situations. We show that urban youth who do not have a specific diagnosed mental illness are more likely than those who have been diagnosed and have received treatment to use Ecstasy to cope with both situational stress and lifetime trauma. Diagnosed and treated youth sometimes self-medicate with other drugs, but do not choose Ecstasy for mediation of their psychological stress. We discuss the implications of self-medication with Ecstasy for mental health services to urban youth experiencing mental health disparities, and for the continued testing and prescription of MDMA for therapeutic use in controlled clinical settings.