This review describes systems-level innovations that may enhance accessibility, economy and integration of treatment services for substance-related disorders. After introducing a conceptual model to describe the resources, qualities and effectiveness of drug treatment services, evidence is reviewed in three areas (primary care, criminal justice, and mental health) that illustrate how systems-level concepts can be used to organize services to maximize their population impact. Special attention is given to systems issues in relation to the development of services in countries of the Eastern Mediterranean Region.