Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and scientific reasons. There have been several prominent papers that have reported limited concordance of animal experiments with subsequent human clinical trials. Recent assessments of the quality of animal studies have suggested that this translational failure may be due in part to shortcomings in the planning, conduct and reporting of in vivo studies. This talk will emphasize methods to assure best practice rigor in animal study methods and reporting. It will introduce the so-called “scientific 3Rs” of Relevance, Robustness, and Reproducibility to the In vivo study approach, and will review important new trends in the pharmaceutical discovery and development communities.