Significant improvements in therapy and life expectancy of β-thalassemia patients in last decades result in the need of commitment for gynecologists and obstetricians as the complexity of organ impairment needs a specific multidisciplinary approach. After a review of clinical manifestations of β-thalassemia from a gynecologic point of view, we present the experience of a gynecologic center in treating β-thalassemia patients from more than 20 years.