Sickle cell disease played a pioneering role in the establishment of the field of molecular medicine. Even though this disease was identified many years ago its clinical course is still not clear. Clinical severity ranges across individuals, even within the same ethnic group. Molecular studies have identified different haplotypes across the globin gene cluster. Correlating individual haplotypes with clinical severity has become the primary focus in the endeavour to establish a successful treatment. Even though numerous studies have been performed, most have shown a negative correlation between beta S-globin haplotypes and clinical phenotype. After a review of recent medical literature, the authors conclude that further research translating genetic analysis to positive therapeutic response for sickle cell disease patients is needed.