Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, emerged in late 2019 and rapidly evolved into a pandemic around the world. The COVID-19 pandemic has dramatically changed the epidemiology and seasonality of other traditional res-piratory viruses e.g., influenza, respiratory syncytial virus, enterovirus, etc. These traditional respiratory viruses share similarity in transmission mode and clinical symptoms with SARS-CoV-2 but may differ in clinical outcomes and management. Co-infection between SARS-CoV-2 and one or more traditional respiratory viruses have been reported in the literature but showed mixed evidence in clinical outcomes. With SARS-CoV-2 evolving into mild Omicron variants, it is believed that SARS-CoV-2 co-circulates with other respiratory viruses, which in return affect the epidemiology and clinical course of respiratory viral infections. In response to these changes, multiplex molecular testings for SARS-CoV-2 and one or more traditional respiratory viruses are attracting more attention in the field and have been developed into a variety of testing modalities. In this review, we describe the epidemiology and clinical significance of traditional respiratory viruses and their co-infection with SARS-CoV-2 in the post-COVID era. Further, we review the principle of multiplex molecular testings and their application to the detection of respiratory viruses and their co-infections. Altogether, this review not only sheds light on epidemiology and clinical significance of respiratory viral infections and co-infections in the post-COVID era and but only provides insights on the laboratory-based diagnosis of respiratory viral infections using multiplex molecular testing.