Coronary artery disease is the leading cause of death in the United States. Serum cholesterol is a widely used screening test to detect persons at high risk for coronary artery disease, including those with familial hypercholesterolemia. However, universal screening of currently healthy persons is not without risk. Previous experience in screening for sickle cell anemia and hypertension has shown that these risks include misunderstanding of test results, misdiagnosis, labeling, stigmatization, and decreased psychological well-being. Results of screening programs may be misused by industry or insurance companies to exclude individuals from positions or benefits. Consideration of these harms suggests that screening should not be implemented until certain safeguards are in place. Physicians and the public should be educated about the potential risks and benefits of screening. Screening tests should be accurate, reliable, valid, and of demonstrated sensitivity. Informed consent for screening should be obtained. Follow-up surveillance and recommended treatments, including dietary counseling and drug therapy, should be available to all individuals identified as being at high risk regardless of their socioeconomic status. Finally, procedures to protect the right to privacy of individuals and their families should be implemented well in advance of the actual screening.