In the United States, the costs associated with diabetes mellitus are increasing. Although people with diabetes comprise less than 6% of the US population, approximately 1 in 5 health care dollars is spent caring for people with diabetes. Healthy lifestyle interventions for the general population and intensive lifestyle and medication interventions for high-risk individuals present opportunities for diabetes prevention. This article describes the costs associated with glucose intolerance and diabetes, the effect of glucose intolerance and diabetes on the quality of life, and the cost-effectiveness of screening and primary prevention interventions for diabetes prevention.