The translation of preclinical drug discover to clinical development has historically suffered a high attrition rate resulting in the majority of clinical studies failing in Phase I and Phase II clinical trials. The reasons for this are as varied and complex as the disease we aim to treat. To combat this, improvements are simultaneously needed in multiple areas; both preclinical and clinical as well as understanding the limitations of certain preclinical models as they relate to human disease. A recent paper by Kimmelman et al. examines guidelines for in vivo experiments in animals in order to help improve the fidelity of preclinical studies. The researchers identified preclinical guidelines that met their predefined eligibility criteria, and offered 55 different recommendations for the design and execution of preclinical in vivo animal studies.