Practice-based research networks (PBRNs)—collaborations of practice settings that work together to generate research knowledge—are underused in mental health services research. This article proposes an agenda for mental health services research that uses a variety of PBRN structures and that focuses on what really happens in practice, the effectiveness of practice innovations in real world care, the challenges of implementing evidence supported interventions, modification of clinician behavior, and assessment of the effect of mental health policy changes on practice. The challenges of conducting research within PBRNs are substantial, including difficulties in maintaining positive member relations, securing ongoing funding, sustaining productivity, overcoming IRB entanglements and achieving both scientific excellence in recruitment and measurement validity and utility for practitioner members. However, the awareness of these challenges allows researchers and practitioners to build networks that creatively overcome them and that infuse mental health services research with heavy doses of the realities of everyday clinical practice.