Purpose To determine whether multivariable risk factor assessment can be as successful in developing disease prevention strategies in patients with ocular hypertension as it has been in patients at risk for coronary heart disease (CHD). Design From a literature review of the evolution of the global risk assessment model for CHD, parallels are drawn to the evolution of a global risk assessment methodology for glaucoma. Methods This article summarizes the literature on global risk assessment and prevention of CHD in clinical practice, discusses the development of glaucoma risk assessment based on available trial and population data, and reviews the potential for prevention strategies founded on the cardiovascular disease model. Results To improve risk assessment in glaucoma and develop disease management strategies for patients with ocular hypertension, it is first necessary to identify and quantify levels of risk associated with factors that predict disease progression. In addition, the incidence of glaucoma and the average person's life expectancy based on his or her age are needed. Finally, it is necessary to quantify how long it takes to develop a visual defect that affects quality of life once a person develops glaucoma. Conclusion The systematic application of epidemiologic data to CHD risk factor models provides insights into how global risk assessment can be incorporated into treatment recommendations for managing individuals with glaucoma. It is hoped that ophthalmologists can use the results of future clinical trials and long-term studies to develop disease prevention strategies in patients with ocular hypertension based on multivariable risk assessment. © 2004 by Elsevier Inc. All rights reserved.