Globally, the zebrafish as an experimental animal has been welcomed and utilization increased successively. Zebrafish is a common name of Danio rerio fish. It belongs to the Cyprinidae family, within the order of the Cypriniformes. The fish is named for the five uniform, parallel blue-colored long narrow bands on the body side. The stripes are extended up to the tail end of the fish. The successful implementation of zebrafish as a trial animal majorly depends upon the key features like its genotypic and phenotypic similarities to human and their easy maintenance at laboratory scale. There is much similarity between the major organ systems like nervous, cardiovascular and digestive systems of human and zebrafish. It is possible to identify and study the physiological and pharmacological responses of drugs and other bioactive compounds with therapeutic value. The zebrafish model is a powerful, well-established research platform for the testing of activities of new drug molecules. The nano-sized materials have opened up various possibilities in a variety of industrial issues and scientific endeavors. Nanomedicines are an effective way of drug delivery systems as they enhance drug absorption by improving the solubility characteristics of the drug. Bioactive nanoparticles can be easily and successfully studied on both embryos and adult zebrafish. Nanoparticles having biological activities like anti-convelsant, anti- melanogenic or other activities which affect the cardiovascular system, nervous system, reproduction system, etc. have been successfully studied on zebrafish as an experimental animal model. The zebrafish also plays an important part in toxicological studies of the nanomedicines. The zebrafish has proven its extensive promises as an in vivo animal model for screening of nanomaterials. The zebrafish can be employed in the process of drug development at the stage of pre-clinical testing. Presently, research is focused on the biological activity testing and toxicological testing of newly developed medicines especially chemotherapeutic agents or nanoparticles used in the treatment of cancer.