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While the current system of care for treating rare but serious infectious diseases—which was developed in response to the 2014–2016 Ebola outbreak—provides an important foundation, a number of issues remain. In particular, a system of care must be able to sustain capacity and capabilities, manage the distribution of needed resources, and meet high demand for services. In this report, RAND researchers consider the need to strengthen the current system of care, discuss potential opportunities, and identify key financial considerations for the sustainability of the system. This research suggests that the United States may benefit from a strengthened or more formalized system of care for rare but serious infectious diseases. The authors identify several opportunities to strengthen the current system of care, including enhancing or building upon the three tiers of acute care facilities that were established during the Ebola outbreak of 2014–2016, developing a brain trust of clinicians and others who can provide advice to health care providers, using mobile teams, and enhancing air and ground systems for safely transferring infected patients. The authors also lay the groundwork for future discussions around key financial considerations to ensure the sustainability of a system of care for rare but serious infectious diseases.