The purpose of this white paper is to provide a succinct summary of the different experimental approaches that have been used in preclinical post-operative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of post-operative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. We have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, our goal is to improve the quality and consistency of post-operative cognitive dysfunction /perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and “best practices” in experimental design and reporting to increase the likelihood of corroborating results. Thus, we conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.