PURPOSE An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC).METHODS Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research.RESULTS Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community.CONCLUSION Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life. INTRODUCTIONM ore than 1 in 4 Americans lives with the burden of more than 1 ongoing health condition, [1][2][3] and the number of persons living with multiple chronic health conditions is growing dramatically. 2,4 Medical costs for persons with chronic illnesses account for 75% of US health care spending, 4 and more than 90% of the Medicare spending on older adults is devoted to persons suffering from multiple chronic conditions (MCC). 5 This heavy expenditure has not yielded the desired increase in quality of life for those affected. 4 A strategic framework of the Department of Health and Human Services (DHHS) 6 and multiple proposals and programs from the private sector highlight the growing concern about persons living with MCC. 261Current health care and research approaches are largely mismatched to the challenge of persons living with MCC. Both health care and research are p...