ABSTRACT Public health nurses in local health departments may receive the first call regarding a potential case of avian influenza, monkeypox, or viral hemorrhagic fever. One public health approach to containing these dangerous infectious disease outbreaks is the use of specialized isolation units. Early access to a biocontainment patient care unit (BPCU) for isolation during a bioterrorism or public health emergency event along with appropriate use of epidemiological and therapeutic interventions in the community may dramatically impact the size and severity of a disease outbreak (Smith et al., 2006). As emerging infectious agents, pandemics, resistant organisms, and terrorism continue to threaten human life; health care and emergency care providers must be empowered to work with nurses and other professionals in public health to plan for the consequences. This article describes the evolution of Nebraska's BPCU strategy for public health preparedness in the face of a biological threat. Design priorities, unit management, challenges, and lessons learned will be shared to guide others in establishing similar infrastructure.