Associations between self-esteem and abuse of alcohol and psychoactive substances have been documented in empirical studies involving high school and college students. No research exists that addresses whether this association generalizes to adult homeless substance users. The current study uses secondary data analysis methodology to evaluate an experimental design study involving 305 homeless men, assigned randomly to the treatment or control group. Control subjects were referred to community-based services. Experimental subjects were exposed to individual and group interventions, life-skills, and relapse prevention training while residing in a 24-hour shelter, for three months. Trained graduate students collected data using standardized questions to interview subjects. Three hypotheses were tested. Hypothesis I that the interventions would contribute toward increased self-esteem at T2, T3, T4 and T5 was not supported. The preponderance of findings pertaining to Hypothesis II, that higher self esteem would be associated with lower alcohol and drug use in treatment subjects, and Hypothesis III, that these associations would be greater among treatment than control subjects over time, were not confirmed, although a few results were consistent with these hypotheses. Overall, results indicated that self-esteem was not increased in treatment subjects despite decreases in alcohol and drug use. The role of self-esteem in this population appears different from its importance in high school and college students. Possible reasons for this apparent difference are explored.