Objective: This paper: (1) explores the real and perceived threats to Emergency Departments (EDs) in addressing infectious disease cases in the US, like measles, and (2) identifies priorities for protecting employees, patients, and others stakeholders through hospital preparedness while streamlining processes and managing costs. Methods: A case study approach was used to describe the events that triggered an infectious disease emergency response in 1 ED in the southeast. Development of the case study was informed by emergency preparedness literature on Homeland Security Exercise and Evaluation Program processes. Results: Hospital staff and administrators identified a number of factors that either positively contributed to disease containment or exacerbated conditions for disease transmission. Successes included early recognition of the potential threat, development of a multidisciplinary taskforce, and implementation of a pre-incident response plan. Challenges comprised of patient flow in crisis response, lab turnaround time, and employee records. Conclusions: The threat of exposure challenged daily operations and raised situational awareness among administrators and providers to issues that might arise during an infectious disease exposure. Recording emergency preparedness successes, remediating challenges, and sharing information with others may help minimize the threat of communicable diseases within hospital settings in the future.