The hemoglobinopathies, including sickle cell disease and its variants, are genetic abnormalities of hemoglobin. Hemoglobin SS (sickle cell disease) is the most common form of hemoglobin mutation in North America. Complications of hemoglobinopathies are numerous and involve many organ systems, including the nervous system. This article is intended to introduce the reader to the epidemiology, diagnosis, treatment, and prevention of neurologic complications of hemoglobinopathies, focusing specifically on sickle cell disease because of its prevalence.