Sickle Cell Disorder (SCD) is a congenital hemoglobinopathy. There is little in literature regarding the psychological variables affecting individuals living with SCD and all of the significant people around them. There are also limited numbers of trained clinical psychologists and genetic counselors to cater for the psychotherapeutic needs of individuals living with SCD. Even among those who have been trained, only a few might have fully grasped the complexities of the disease pathology. Early understanding of its pathological nature, sources, types, complications, pathophysiological basis, and clinical severity of symptoms among clinical psychologists, genetic counselors and psychotherapists, as well as general medical practitioners, could guide them in providing holistic care for dealing with and reducing pain among individuals living with SCD. It could allow risk-based counseling for families and individuals. It could also justify the early use of disease-modifying or curative interventions, such as hydroxyurea (HU), chronic transfusions (CTs), or stem-cell transplantation (SCT) by general medical practitioners. Hence, the need for this paper on the pathophysiology of SCD.