The laboratory mouse was domesticated from fancy mice that arose from geographically diverse genetic origins. The diverse origins of the mouse also contributed to a lengthy list of infectious agents that are carried by mice. Despite years of microbial quality control, the burgeoning use of mice for research is causing a resurgence of infectious disease among laboratory mice. Infections can be introduced through mice, but also through biologic products such as serum, hybridomas, and transplantable tumors and through iatrogenic introduction by scientists. Retroviruses represent an important group of agents with significant effects upon mouse research, but the transmissible exogenous viruses are no longer an issue among laboratory mice. The diversity of other infectious agents induce a wide variety of effects upon cancer research, including immunomodulation, tumor graft rejection, misinterpretation of phenotype, modified carcinogenesis, and zoonotic risk. Prudent research practices require that microbial status of research mice does not necessarily have to be standardized among laboratories, but it must be defined so that research results are reproducible and valid.