At first blush, an outbreak of mouse hepatitis virus or epizootic diarrhea of infant mice virus in a research colony of laboratory mice may not seem like a disaster. However, irrespective of magnitude, such an outbreak at an academic institution is disruptive for researchers at all levels. It can be a disaster for the graduate student who may have just a few experiments to finish before writing the thesis or for the postdoctoral fellow who is in the lab for only 1 or 2 years. Infectious disease outbreaks also limit the ability of principal investigators to share their animals with collaborators at their home institution as well as with those at extramural sites, thereby thwarting the expectation that research materials supported by federal funds will be made readily available to colleagues. This article traces the evolution of a change in culture at a large, well-funded academic institution with over 1,800 active IACUC protocols, more than 1,000 of which include mice. During a period of less than 5 years, the institution evolved from virtual paralysis in the face of such outbreaks to the implementation of policies and practices that enable effective outbreak management and the timely resumption of research functionality. This evolution required not only support from the highest levels of leadership in the university and its school of medicine but also a huge outlay of financial resources.