Background: More than 20 years ago the Institute of Medicine advocated for integration of physical and behavioral health care. Today, practices are integrating care in response to recent policy initiatives. However, few studies describe how integration is accomplished in real-world practices without the financial or research support available for most randomized controlled trials.Methods: To study how practices integrate care, we are conducting a cross-case comparative, mixedmethods study of 11 practices participating in Advancing Care Together (ACT). Using a grounded theory approach, we analyzed multiple sources of data (eg, documents, practice surveys, field notes from observation visits, semistructured interviews, online diaries) collected from each ACT innovator.Results: Integration requires making changes in organization and interpersonal relationships. During early integration efforts, challenges related to workflow and access, leadership and culture change, and tracking and using data to evaluate patient-and practice-level improvement emerged for ACT innovators. We describe the strategies innovators are developing to address these challenges.