The last two decades have witnessed the emergence of three deadly coronaviruses (CoVs) in humans: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are still no reliable and efficient therapeutics to manage the devastating consequences of these CoVs. Of these, SARS-CoV-2, the cause of the currently ongoing coronavirus disease 2019 (COVID-19) pandemic, has posed great global health concerns. The COVID-19 pandemic has resulted in an unprecedented crisis with devastating socio-economic and health impacts worldwide. This highlights the fact that CoVs continue to evolve and have the genetic flexibility to become highly pathogenic in humans and other mammals. SARS-CoV-2 carries a high genetic homology to the previously identified CoV (SARS-CoV), and the immunological and pathogenic characteristics of SARS-CoV-2, SARS-CoV, and MERS contain key similarities and differences that can guide therapy and management. This review presents salient and updated information on comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of SARS-CoV, MERS-CoV, and SARS-CoV-2; this can help in the design of more effective vaccines and therapeutics for countering these pathogenic CoVs.