Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide in terms of frequency and social impact, recently recognized as a global public health problem by the World Health Organization. It is a monogenic but multisystem disorder with high morbidity and mortality. Vaso-occlusion, hemolytic anemia and vasculopathy are the hallmarks of SCD pathophysiology. This review focuses both on "time-dependent" acute clinical manifestations of SCD and chronic complications commonly described in adults with SCD. The review covers a broad spectrum of topics concerning current management of SCD targeted at the internists and emergency specialists who are increasingly involved in the care of acute and chronic complications of SCD patients.