Sickle cell syndromes are a group of inherited disorders of haemoglobin structure that have no cure in adults at the present time. Bone marrow transplantation in children has been shown to be curative in selected patients. The phenotypic expression of these disorders and their clinical severity vary greatly among patients and longitudinally in the same patient. They are multisystem disorders and influence all aspects of the life of affected individuals including social interactions, family relations, peer interaction, intimate relationships, education, employment, spiritual attitudes and navigating the complexities of the health care system, providers and their ancillary functions. The clinical manifestations of these syndromes are protean. In this review emphasis is placed on four sets of major complications of these syndromes and their management. The first set pertains to the management of anaemia and its sequelae; the second set addresses painful syndromes both acute and chronic; the third set discusses infections; the fourth section deals with organ failure. New experimental therapies for these disorders are briefly mentioned at the end. Efforts were made to include several tables and figures to clarify the message of this review.