Plague, caused by the bacterium Yersinia pestis, continues to cause disruptive and deadly outbreaks. It is also considered a Tier 1 Select Agent, the highest level of bioterrorism threat, by the U.S. Department of Health and Human Services. The May 2020 Clinical Infectious Diseases supplement shares nine manuscripts organized by the Centers for Disease Control and Prevention with data from systematic literature reviews, U.S. plague surveillance, and animal research. The articles bring together an evidence base on the treatment of plague and considerations for special populations with an aim of increasing resilience and national security against plague by advancing scientific and medical knowledge in order to inform preparedness.