This article proposes methodological strategies that, if used in treatment outcome research, may help in the transition of efficacy research findings into effectiveness trials in clinical and service delivery settings. Alternative methodologies are proposed to examine how treatment effectiveness may vary as a function of degree of treatment structure, treatment protocol compliance, psychotherapy integration into an overall treatment regimen, participant selection and composition, and variations in treatment parameters. The discussion focuses on encouraging the retention of experimental control while stretching psychotherapy outcome research designs to encompass effectiveness issues.