Hemoglobinopathies are diseases involving abnormalities of the structure or production of hemoglobin. Examples include sickle cell disease, the thalassemias, and rare hemoglobin variants producing cyanosis. Recent advances in the understanding of the consequences of hemoglobin dysfunction on nitric oxide signaling have led to a reassessment of the pathophysiology of sickle cell disease and thalassemia. Chronic vascular inflammation and damage is now recognized as playing an important role in disease expression. Hemoglobinopathies may present to the anesthesiologist as the primary cause of a surgical procedure, as an incidental complicating factor of a surgical patient, or with a problem arising from the disease itself. This article reviews the common types of hemoglobinopathies, presents a basic summary of the pathophysiology relevant to anesthesia, and outlines current perioperative management.