Cooley's anemia, or thalassemia major, is a blood disorder characterized by a marked increase in F hemoglobin and a decrease in the production of certain oxygen-carrying proteins in red blood cells. Thalassemia major is the most severe form of the chronic familial anemias that result from the premature destruction of red blood cells and is inherited as an autosomal recessive trait. The molecular mechanisms responsible for the switch from fetal hemoglobin to adult hemoglobin production have been further clarified, while new drugs to enhance the production of fetal hemoglobin and relieve the anemia of thalassemia have been introduced and studied. Understanding of the relationship between molecular genotype and clinical phenotype has been advanced, and the techniques for molecular diagnosis, including prenatal diagnosis, have been vastly improved. Most importantly, there have been dramatic improvements in the treatment and prevention of complications of thalassemia.