Previous severe acute respiratory syndrome-coronavirus (SARS-CoV) outbreaks resulted in a cohort of preclinical studies that utilized various mice models for determining the pathogenesis of the infection, including the viral replication, spread, and mortality of the disease. Such studies have provided a framework upon which new investigations have been launched for understanding the outbreak of new coronavirus disease-19 (COVID-19) causing viral agents and their interaction with the host and its body. Recent investigations showed that the previous SARS-CoV and the recently discovered severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) both require the spike S protein to enter the host cell upon infection the binding with the receptors on the surface of the cells. The viral entry also requires proteases from the host cells. Since there are key similarities between the structure of the viruses and the construct of the viral transmission along with the spread inside the host's body in animal models. They were developed for the previous viral agent. The disease can be emulated or manipulated to bring forth novel investigations leading to key data that can broaden the sphere of COVID-19 studies being conducted. There are several different options to choose the right animal model for the question being raised in the experimental design with the pathogenesis of COVID-19. This chapter focused on the already established animal models for other coronavirus outbreaks and some of the strategies that can be exploited to develop new animal models. For COVID-19, research aimed at targeting the therapy or basic investigations for understanding cellular or organ level mechanisms involved in the disease.