Most healthcare quality improvement and cost reduction efforts currently focus on care processes, or transitions—for example, the hospital discharge process. While identification and adoption of best practices to address these aspects of healthcare are essential, more is needed for systems that serve vulnerable populations: to account for social factors that often inhibit patients’ ability to take full advantage of available healthcare. Our urban safety net healthcare system developed and implemented an innovative quality improvement approach. The programs, Guided Chronic CareTM, and Passport to Wellness, use Assertive Care and provide social support for patients between medical encounters, enabling patients to make better use of the healthcare system and empowering them to better manage their conditions. Results: The majority of patients reported problems with mobility and nearly half reported anxiety or depression. Early indications show improved quality of care and significant reduction in costs. Challenges encountered and lessons learned in implementing the programs are described, to assist others developing similar interventions.