Respiratory viral coinfections pose a significant global public health threat, causing economic burdens on individuals, families, and healthcare systems. These coinfections can occur when two or more respiratory viruses infect the same host, leading to synergistic or antagonistic interactions that affect viral replication rates. The prevalence of coinfections varies based on geographical location, seasonality, patient demographics, and circulating viruses. Studies have shown that about 10-20% of respiratory viral infections involve multiple coinfections, with some combinations causing altered disease outcomes and others having no impact. The recent COVID-19 pandemic has highlighted the importance of understanding respiratory viral coinfections, as many studies have reported severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) coinfections with other respiratory viruses, which have been associated with poor disease outcomes and increased hospitalization rates. The impact of respiratory viral coinfections on disease severity and outcome is complex and multifaceted. Some coinfections can increase viral load, while others can inhibit viral replication. The order of virus infection and the genetic diversity of viruses can influence the immune response and disease progression. For example, RSV pre-infection can protect against subsequent IAV infection, while IAV pre-infection can enhance SARS-CoV-2 infection. The immune response during coinfections is also complex, with cytokine production and chemokine induction patterns varying depending on the virus combinations. Experimental models, such as animal models (mice, hamsters, and ferrets) and in vitro cell culture systems (primary human epithelial cells and lung organoids), have been crucial in studying the dynamics and immune modulation of respiratory viral coinfections. These models help in understanding the pathogenesis, immune response, and disease outcomes, which are essential for developing effective diagnostic and therapeutic strategies. Future research should focus on improving diagnostic methods for respiratory viral coinfections, developing more physiological models, and understanding the long-term effects of coinfections to design targeted antiviral therapies. Insights from these studies will enhance our ability to combat the effects of coinfected viruses in the respiratory tract.Respiratory viral coinfections pose a significant global public health threat, causing economic burdens on individuals, families, and healthcare systems. These coinfections can occur when two or more respiratory viruses infect the same host, leading to synergistic or antagonistic interactions that affect viral replication rates. The prevalence of coinfections varies based on geographical location, seasonality, patient demographics, and circulating viruses. Studies have shown that about 10-20% of respiratory viral infections involve multiple coinfections, with some combinations causing altered disease outcomes and others having no impact. The recent COVID-19 pandemic has highlighted the importance of understanding respiratory viral coinfections, as many studies have reported severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) coinfections with other respiratory viruses, which have been associated with poor disease outcomes and increased hospitalization rates. The impact of respiratory viral coinfections on disease severity and outcome is complex and multifaceted. Some coinfections can increase viral load, while others can inhibit viral replication. The order of virus infection and the genetic diversity of viruses can influence the immune response and disease progression. For example, RSV pre-infection can protect against subsequent IAV infection, while IAV pre-infection can enhance SARS-CoV-2 infection. The immune response during coinfections is also complex, with cytokine production and chemokine induction patterns varying depending on the virus combinations. Experimental models, such as animal models (mice, hamsters, and ferrets) and in vitro cell culture systems (primary human epithelial cells and lung organoids), have been crucial in studying the dynamics and immune modulation of respiratory viral coinfections. These models help in understanding the pathogenesis, immune response, and disease outcomes, which are essential for developing effective diagnostic and therapeutic strategies. Future research should focus on improving diagnostic methods for respiratory viral coinfections, developing more physiological models, and understanding the long-term effects of coinfections to design targeted antiviral therapies. Insights from these studies will enhance our ability to combat the effects of coinfected viruses in the respiratory tract.