Sickle cell disease is the most common of the clinically significant hemoglobinopathies. In the United States, the disease and trait occur almost exclusively among African Americans. Sickle cell disease afflicts 1 in 375 African Americans and 1 in 60,000 whites. During the late 1960s and early 1970s, sickle cell disease received a great deal of attention in the medical and lay press. The importance of screening for the disease and trait was stressed. Some states legislated mandatory adult screening programs. All but a few states have focused screening efforts on newborns. As a result, sickle cell disease (the hemoglobin SS homozygous state) is now usually identified through state-sponsored universal screening programs. Children in whom anemia is not identified by screening present later with impaired growth, increased susceptibility to infection, or painful crisis. Screening of adults is aimed at the identification of asymptomatic carriers of sickle cell trait (the hemoglobin AS heterozygous state). The principal objective is to reduce the prevalence of the homozygous condition by means of genetic counseling. Whether screening benefits the people screened has been debated. Screening can be harmful without subsequent effective education and counseling that allows for informed decisions to be made about pregnancy and prenatal diagnosis. An understanding of the natural history of sickle cell trait and disease, sensitivity to the concerns of affected patients, and selective use of screening tests are all necessary if such harmful effects are to be avoided.