Sickle cell anemia is an inherited disorder of the globin chains that causes hemolysis and chronic organ damage. Sickle cell anemia is the most common form of sickle cell disease (SCD), with a lifelong affliction of hemolytic anemia requiring blood transfusions, pain crises, and organ damage. Since the first description of the irregular sickle-shaped red blood cells (RBCs) more than 100 years ago, our understanding of the disease has evolved tremendously. Recent advances in the field, more so within the last three decades, have alleviated symptoms for countless patients, especially in high-income countries. Although there is evidence of several important therapies in the pipeline, greater investment in research is needed into both of these therapies and the dissemination of effective care to the affected population, especially because of historical mistrust. In this book, we present an overview of sickle cell disease, pathogenesis, clinical presentation, complications, and recent treatment modalities and prospective research that will enable the reader to get a better understanding of this hot topic.