Hemoglobinopathies are the most common single-gene disorders in the world. Their prevalence is predicted to increase in the future, and low-income hemoglobinopathy-endemic regions need to manage most of the world's affected persons. International organizations, governments, and other stakeholders have initiated national or regional prevention programs in both endemic and nonendemic countries by performing population screening for α- and β-thalassemia, HbE disease, and sickle cell disease in neonates, adolescents, reproductive-age adults (preconceptionally or in the early antenatal period), and family members of diagnosed cases. The main aim of screening is to reduce the number of affected births and, in the case of sickle cell disease, reduce childhood morbidity and mortality. Screening strategies vary depending on the population group, but a few common screening test methods are universally used. We discuss the salient features of population-screening programs around the globe as well as current and proposed screening test methodologies.