Hemoglobinopathies are the most common inherited red cell disorders worldwide among which thalassemias and sickle cell syndromes constitute the two main groups. The hemoglobinopathies are commonly diffused in areas where malaria was endemic, due to the fact that mutated genes caused protection against malaria. In this review, we will present some cases of patients affected by thalassemia major, transfusion-dependent thalassemia (TDT), thalassemia intermedia, non-transfusion-dependent thalassemia (NTDT), and sickle cell disease (SCD), followed by questions and discussion about most of their clinical problems and their management, based on Thalassemia International Federation (Thalassemia International Federation. Guidelines for the management of transfusion dependent thalassaemia (TDT). 5th ed, 2025) and National Institutes of Health (National Institutes of Health. The management of sickle disease. NIH publications no. 02-2117. 4th ed, 2002) Guidelines. The discussion leads to an overview of the diseases presented, and it is an opportunity for readers to look for a more comprehensive evaluation of patients with different forms of hemoglobinopathies.