The recent emergence of the novel betacoronavirus, pathogenic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) with high nucleotide identity to SARS-CoV represents the causative agent of a potentially deadly disease coronavirus disease-19 (COVID-19) in Wuhan, China, and spreading across several countries globally pose a great global public health concern. Until a vaccine is available, effective therapy must be identified, and many clinical trialshave been executed worldwide. Various in vitro investigations are ongoing using different cell cultures to find alternative treatment options, allowing SARS-CoV-2 replications. Various cell lines are susceptible to the SARS-CoV-2 infection. In this chapter, literature regarding SARS-CoV-2 isolated in several cell lines commonly used for diagnostic or research purposes has been summarized. It also shows that SARS-CoV-2 can achieve high titers in various cell cultures derived from different species. In addition, these cell lines are extensively used in the diagnosis, to study pathophysiology, genome studies, and the finding of new targets for drug development and provide new ideas for the discovery of lead compounds with potential therapeutic agents against novel COVID-19.