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Acute chest syndrome (ACS) in sickle cell disease (SCD) is a serious condition that carries with it a high rate of morbidity and mortality. This review highlights the pearls and pitfalls of ACS in SCD, including diagnosis and management in the emergency department (ED) based on current evidence. ACS is defined by respiratory symptoms and/or fever and a new radiodensity on chest imaging in a patient with SCD. There are a variety of inciting causes, including infectious and non-infectious etiologies. Although ACS is more common in those