Sickle cell disease is one of the most common monogenic causes of hemolytic anemia worldwide. The main pathophysiology is based on the single nucleotide polymorphism resulting in hemoglobin polymerization leading to sickle red blood cells. The sickled red blood cell will produce vaso-occlusion affecting multiple organs and this is the clinical hallmark of sickle cell disease. The repeated episodes of vaso-occlusion lead to damages to many organs including the brain, the bones, kidneys lungs, etc. The approval of Hydroxyurea for management of sickle cell disease by FDA in 1998 marked a major pharmacotherapeutic milestone in treatment of Sickle cell disease. Hydroxyurea was found to significantly reduce the incidence of Vaso-occlusive crisis, acute chest syndrome and need for blood transfusion. Hydroxyurea is an anti-neoplastic drug and the side effects and toxicity of hydroxyurea in pregnancy and lactation has been documented in preclinical animal studies. This has generated a lot of concern about the safety of Hydroxyurea in pregnant and lactating women. Many anecdotal and accidental use of Hydroxyurea in pregnant women has not validated the toxicity claims in animal studies. Hydroxyurea offers a lot of advantages in reducing the mortality and morbidity associated with sickle cell disease. There is hesitancy on the part of most healthcare workers managing pregnant and lactating sickle cell disease patients to accept the use of Hydroxyurea in pregnancy because of the safety concern. More retrospective data need to be collected as it is not ethically acceptable to do randomized control trials to validate the safety of hydroxyurea in pregnancy and lactation.