Rising health care costs in the United States have created the need to identify prevention and treatment strategies that are both effective and economical. Decision modeling studies aim to help policy makers, organizational leaders, and clinicians quantify and compare prospective costs and benefits of interventions in standardized ways. But health care system operations, patients’ behaviors, and clinicians’ behaviors are extremely complex and hard to accurately predict. Good analysis of what models yield requires identifying which assumptions should shape clinical practice decisions and patients’ health care experiences.