Emergency providers are likely to encounter sickle cell disease–related emergencies. The pathophysiology of emergent complaints are usually related to either an acute anemia or a vasoocclusive crisis. Differentiating between the two is the first step in the workup. Anemic crises must then be differentiated by the source. Vasoocclusive crises must be appropriately treated with aggressive pain management, gentle hydration, and other appropriate adjuncts. Early recognition and treatment are key in providing excellent emergency care to those with sickle cell disease.