This article provides an overview of the major findings of psychotherapy research and discusses the possible implications of these findings for substance user treatment researchers and practitioners. While the centrality of relationship for human change processes was historically understood, twentieth century research tended to see relationship and person variables as secondary to operationalized "mechanisms of action" unique to particular psychotherapies. Interestingly, recent meta-analytic investigations have uncovered the weakness of randomized controlled trials (RCT) comparison investigations that have, until recently, represented the "gold standard" for the field. There has been a resurgent interest in the "common factors" that appear to be important across many effective psychotherapies. In addition, psychiatric anthropologists have contributed important information about the problems of client noncompliance with mental health treatment that parallel quantitative investigations. Substance misuse researchers have also found that client characteristics, especially clients' readiness to engage treatment, are important to investigate. The importance of the "therapeutic alliance" and the characteristics of clients and clinicians have become central areas for study, rather than variables to be controlled or excluded. Emphasis on these factors may represent the future for research in psychotherapy and substance user treatment, especially if researchers and community practitioners can join together to overcome methodological feasibility and dissemination problems that plague effectiveness research. However, the continued attractiveness of comparative studies and treatment efficacy studies may represent longstanding epistemological assumptions and responses to economic incentives that will be difficult to challenge.