This study investigates the therapeutic orientations of substance abuse social workers and the relationship between these orientations and burnout. Ninety-two social workers who provided outpatient treatment to people suffering from substance abuse disorders in Israel participated in the study. The results obtained demonstrated that among substance abuse social workers the psychodynamic and ecosystems therapeutic orientations were more prominent than the cognitive-behavior orientation. A greater adherence to the cognitive-behavior orientation was associated with a higher sense of professional efficacy; a greater adherence to the psychodynamic orientation was associated with a higher level of exhaustion; and greater adherence to the ecosystems orientation was associated with lower levels of exhaustion and cynicism. Females reported lower levels of exhaustion and cynicism. The cognitive-behavioral orientation mediated the connection between the social workers' experience in the field of substance abuse and two dimensions of burnout - exhaustion and professional efficacy. Significance of the findings for improving the well-being of substance abuse social workers and for the advancement of psychosocial services is discussed.