In 2006 the Indian Health System, through the Chronic Care Initiative, developed a partnership with the Institute for Healthcare Improvement to use modern improvement methodologies to fundamentally transform the system of care for clinical prevention and management of chronic conditions for American Indian and Alaska Native people. This article describes the accomplishments of the initiative thus far, including consistent improvement in alcohol misuse screening, colorectal cancer screening, and childhood immunizations; decreasing office visit cycle time; and improved continuity of care.