Sickle cell anemia is a genetic blood disorder arising from a point mutation in 
the beta-globin gene that leads to the replacement of glutamic acid residue by 
valine at the sixth position of the beta--chain of hemoglobin. At low oxygen 
tension, the mutant hemoglobin, sickle hemoglobin, polymerizes inside the red 
blood cells into a gel or further into fibers leading to a drastic decrease in 
the red cell deformability. As a result, micro-vascular occlusion arises which 
may lead to serious, sometimes fatal, crises. The present article reviews the 
historical, genetic, molecular, cellular, and clinical aspects of the disease. A 
review for the development and design of drugs to treat sickle cell anemia is 
presented. Anti-sickling agents are classified, based on the target to be 
modified, into three classes: the gene, the sickle hemoglobin molecule, and the 
red cell membrane modifiers. In spite of the full understanding of the 
pathology, physiology, and the molecular nature of the disease, and the 
development of large number of antisickling agents, a cure for sickle cell 
anemia still is unavailable. Strategies to treat sickle cell anemia since the 
early times of the disease state discovery in 1910, has focussed mainly on 
prophylactic measures to alleviate the painful crises. The article addresses 
clinical approaches used then and now to treat the disease, and the rationale of 
their use. Currently in clinical practice, hydroxyurea is the most commonly used 
agent to treat the disease, and it has been recently approved by the united 
states Food and Drug Administration as a drug for that purpose.