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Coronavirus disease 2019 (COVID-19) now needs no certain introduction. The whole world is working on the various possibilities involving therapeutic agents to combat COVID-19. Based on the mechanism of COVID-19 causing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pathogenesis, numbers of mediators have been proposed to date. However, considering those mediators for the treatment does not provide any satisfactory result and thus they have not been approved for treating COVID-19, to date. Consequently, even obtaining a promising treatment to combat this pandemic, detecting SARS-CoV-2 along with identifying the infected patients will remain the utmost priority. Since its symptoms are similar to that of the patients of other respiratory infections, differential diagnosis becomes very important. Differential diagnosis distinguishes a specific disease or disorder from others that trail analogous medical symptoms. This book chapter provides a detailed study regarding the differential diagnostic techniques for COVID-19 with updated knowledge and illustrations.