In science it is imperative that the basic reagents and materials are defined and uniform. Unlike chemical reagents, which are uniform over time, mice, like all living creatures, have an intrinsic genetic drive to change, with mutations accumulating over time leading to increasing genetic variation and phenotypic change. Such changes compromise the reproducibility of experimental data over time and place. The use of the mouse has expanded rapidly in recent years and many scientists who have turned to the mouse as a research model might be unaware of the profound impact of changes in genetic background. Here we discuss the sources of genetic change and strategies to reduce them with the idea of strengthening international genetic standards for inbred mice.