 This article discusses the shift in biomedical research models from rats to mice over the past two decades. The primary reason for this change is the availability of a larger genetic toolbox for mice, specifically embryonic stem cell-based targeting technology for gene disruption. However, recent advancements in genome editing technologies have closed the technological gap between rats and mice, making it important to consider their physiological, anatomical, biochemical, and pharmacological differences when choosing a model system for a specific biological question. The article focuses on neuropsychiatric disorders and highlights the impact of these differences on studies of human diseases. This article was authored by Bart Ellenbrook and June Yuen.