Background: Research during the past few decades has greatly advanced our understanding of the cost, quality, and variability of medical care at the end of life. The current health-care policy debate has focused considerable attention on the unsustainable rate of spending and wide regional variation associated with medical treatments in the last year of life. New initiatives aim to standardize quality and reduce over-utilization at the end of life. We argue, however, that focusing exclusively on medical treatment at the end of life is not likely to lead to effective health-care policy reform or reduce costs. Specifically, end-of-life policy initiatives face the challenges of political feasibility, inaccurate prognostication, and gaps in the existing literature. Objectives: With the ultimate aim of improving the quality and efficiency of care, we propose a research and policy agenda guided by a new conceptual framework of factors associated with treatment intensity for patients with serious and complicated medical illness. This model not only expands the population of interest to include all adults with serious illness, but also provides a blueprint for the thorough investigation of the diverse and interconnected determinants of treatment intensity. Conclusions: The new conceptual framework presented in this paper can be used to develop future research and policy initiatives designed to improve the quality and efficiency of care for adults with serious illness.