Long-term follow-up of cohorts of patients treated in high-income countries has shown a progressive improvement in life expectancy. Myocardial toxicity from iron overload has been the major cause of mortality; however, there has been a substantial decline in cardiac deaths in recent years, related to switching high-risk patients from subcutaneous desferrioxamine to chelation regimes which include the oral chelator deferiprone. The role of deferasirox in enhancing life expectancy is yet to be determined, but it is reasonable to expect an improvement compared with past experience with desferrioxamine. Other causes of mortality will become an increasingly important issue for older thalassemic patients: Surveillance, prophylaxis, and prompt treatment of infection remains essential, and chronic hepatitis virus infection should be managed with best available current therapies. More data on follow-up of thalassemic patients in middle income countries are needed to demonstrate a similar trend in improved survival. The life expectancy for those in low-income countries is similar to the situation 50 years ago in Europe and the United States. The global thalassemia and public health community should consider how to respond to this disparity.