The ability to apply findings from animal studies efficiently and effectively is predicated on an understanding of biology and pathobiology, how that biology relates to the human systems being modeled, and how the studies are conducted and reported. This overview discusses various factors in research within the animal environment (referred to as extrinsic factors) that the NIH now expects to be documented to foster replicability in science and expand interpretations of study outcomes. Specifically, an important extrinsic factor in research with animals is that of individual personnel who perform handling practices, participate in research interactions, and share an overall presence in the housing facility with animals, all of which can confound reproducibility efforts in biomedical science. An improved understanding of the influences and behaviors of animal research personnel on animal responses is critical with regard to research results and the interpretation of data collected from animal models of biomedical disease.