Danio rerio, commonly known as zebrafish, has turned out to be an extremely useful model organism for studying disease mechanisms and conducting medical research. This versatile organism exhibits rapid development, transparent embryos, allowing direct observation of organogenesis and cell fate, and shares notable genetic and physiological similarities with humans, making it an ideal candidate for biomedical research. This chapter will explore the history of zebrafish, providing an in-depth examination of zebrafish as a model organism. Approximately 70% of the zebrafish genome is similar to that of humans, and almost 84% of genes that are known to be associated with human diseases have orthologs in zebrafish. A comprehensive literature review will discuss the role of zebrafish as models for studying a wide range of diseases, from cancer to neurological conditions, highlighting their utility in medical advancements and drug discovery. The chapter will also compare zebrafish with other model organisms, such as rodents and Drosophila, emphasizing the advantages of using zebrafish in research. Additionally, ethical considerations surrounding zebrafish studies, along with best practices for their husbandry and maintenance, will be addressed. Lastly, the chapter will review the prospects of using zebrafish to understand complex human disease models, contribute to advancements in medicine, and aid in therapeutic drug discovery.