The natural history of thalassemia has shown substantial change during these years. This applies for each aspect of the pathology (for example, endocrinological, hepatological and psychological) and also for the pathology that has presented and still presents the main cause of death: myocardial dysfunction. In this review, the pathophysiology of cardiac complications, possible role of myocarditis, new knowledge on pathogenesis, and noninvasive detection methods for iron overload in the heart are pointed out. Prophylaxis of cardiomyopathy and new therapy strategies of myocardial dysfunction, including the impact of the new chelation treatment, are discussed.