The number of disorders associated with congenital or acquired asplenia and functional hyposplenism has increased substantially over the past couple decades. Previously, screening for asplenia and hyposplenism was a barrier to identifying patients at risk. Recent methods for measuring splenic function have emerged as accurate and reliable. Identifying patients prevents overwhelming postsplenectomy infection or invasive pneumococcal disease. Approaches to protect patients with asplenia or hyposplenism include patient education of risks and signs/symptoms of infection, vaccination, and antibiotic prophylaxis. Physicians have evaluated methods of preserving splenic function after trauma and sought alternative treatments of refractory cytopenias treated with splenectomy in the past.