Mice are indispensable in biomedical research due to their genetic, physiological, and anatomical similarities to humans, short generation time, and genetic manipulability. This chapter outlines the advantages that make mice the preferred model organism, including small size, ease of handling, cost-effectiveness, and the availability of diverse genetically modified strains such as transgenic, knockout, and knock-in models. We describe major types of mouse models: inbred, outbred, and genetically engineered, and their specific applications in studying diseases, including cancer, cardiovascular, neurological, infectious, metabolic, autoimmune, and inflammatory disorders. Key examples illustrate how mouse research has contributed to advances in disease understanding, therapeutic development, and preventive strategies. Ethical considerations are addressed with emphasis on the 3Rs (Replacement, Reduction, and Refinement) and global regulatory frameworks guiding humane animal use. Proper housing, husbandry, and welfare practices are discussed for ensuring reliable and ethically sound results. The chapter also highlights emerging mouse-specific alternative methods that can complement in vivo studies. By integrating scientific rigor with ethical responsibility, mice continue to serve as a cornerstone of biomedical research, enabling discoveries that enhance our understanding of human health and inform the development of effective treatments.