Little is known about how to integrate primary care with mental/behavioral services outside of clinical trials. The authors implemented a collaborative care model (CCM) for depression in a safety net patient-centered medical home. The model focused on universal screening for symptoms, risk stratification based on symptom severity, care management for intensive follow-up, and psychiatry consultation. CCM increased rates of primary care physician encounters, timely follow-up for monitoring symptoms of depression, and documentation of treatment response. Contextual factors that facilitated or hindered practice redesign included clinic leadership, quality improvement culture, staffing, technology infrastructure, and external incentives/disincentives for organizational change.