In countries where major animal research is conducted, comprehensive laws exist to ensure that the animals’ physical needs are satisfactorily met. However, animals also require an environment that allows them to fulfill their behavioral needs; this will be the focus of the article. Two studies are described in detail, one on rats and the other on genetically modified mice, which were performed by the author to compare the effects of enriched and un-enriched cage environments on rodent physiology. Evidence is presented showing that if research rodents are housed in cages lacking structures that allow them to perform their normal behaviors, this can lead to significant changes in their physiology and pathology, possibly leading to erroneous and/or oversimplified interpretations of scientific data. The question of whether lack of enrichment impairs the wellbeing of research rodents is also discussed.