Sickle cell anemia is an inherited hemoglobinopathy caused by the presence of hemoglobin S, which lowers the solubility and through the process of polymerization results in sickle erythrocytes obstructing the microvascular network. This entity is characterized by episodes of ischemia-reperfusion injury to vital organs, contributing to its dysfunction. The advent of inducing fetal hemoglobin therapy associated with antibiotic prophylaxis has allowed prolonged survival. However, by increasing longevity, cardiovascular complications are evident, with the development of systemic vascular disease, acute myocardial infarction, pulmonary arterial hypertension and left ventricular dysfunction. The aim of this paper is to review the pathophysiology and treatment of major cardiovascular events in patients with sickle cell anemia.