Sickle-cell anemia is a genetic blood disease characterized by a hemoglobin gene mutation. The genetic failure is basically constituted by replacement of the hemoglobin beta chain in the sixth position so that the amino acid valine is encoded instead of glutamic acid. As a result, the erythrocytes have their normal biconcave discoid shape distorted, generally presenting a sicklelike shape, which reduces both their plasticity and lifetime. Because a complete blood supply is so important during application of both intraoral and extraoral forces, this article addresses the general and oral aspects associated with sickle-cell anemia. This will guide the clinician regarding such patients who seek orthodontic treatment by making references to literature on multidisciplinary management.