The nonclinical studies form the important part of drug development. There are number of factors one needs to consider while planning and executing nonclinical studies that include validation of model, fulfilment of good laboratory practice guidelines, and the regulatory requirements. The Institutional Animal Ethics Committee permission is required before carrying out the experimental work. The animal ethical principles of 4Rs must be adhered that include reduction, replacement, refinement, and rehabilitation of animals. Though the regulations have started promoting the use of alternatives to experimental methods to generate data in this regard. The in silico methods, organoids and organ on chip methods, cell culture techniques, etc., still have to undergo validation in order to make use of them routinely in drug development.