Respiratory viral coinfections are a significant global public health issue, contributing to increased morbidity and mortality, particularly in vulnerable populations. These infections occur when two or more respiratory viruses infect the same host, leading to complex interactions that can either synergistically enhance or antagonistically inhibit viral replication. Understanding these interactions is crucial for accurate diagnosis and effective treatment strategies. This review explores the epidemiology, pathology, immune response modulation, and clinical outcomes of respiratory viral coinfections, emphasizing the importance of experimental models in elucidating the dynamics of these infections. Respiratory viral coinfections are common, with approximately 10–20% of all respiratory infections involving multiple viruses. Studies show that coinfections can alter disease outcomes, with some cases leading to more severe symptoms and increased hospitalization rates. Common coinfection combinations include influenza A virus (IAV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), rhinovirus (RV), human metapneumovirus (HMPV), and human parainfluenza virus (HPIV). The prevalence of these coinfections varies by region, season, and demographic factors, highlighting the need for comprehensive surveillance and targeted prevention strategies. The immune response to respiratory viral coinfections is complex, with interactions between viruses influencing cytokine production and immune cell activation. Some viruses can enhance the replication of others, while others may inhibit viral replication or modulate immune responses. Experimental models, such as mice, hamsters, and ferrets, are essential for studying these interactions, as well as in vitro models like air-liquid interface cultures and lung organoids. These models help researchers understand the pathogenesis and immune modulation associated with coinfections. Future research should focus on improving diagnostic methods, understanding the mechanisms of viral interactions, and developing targeted interventions to mitigate the severity of respiratory viral coinfections. Advances in genomic surveillance and mathematical modeling can further enhance our understanding of these complex interactions, leading to more effective prevention and treatment strategies.Respiratory viral coinfections are a significant global public health issue, contributing to increased morbidity and mortality, particularly in vulnerable populations. These infections occur when two or more respiratory viruses infect the same host, leading to complex interactions that can either synergistically enhance or antagonistically inhibit viral replication. Understanding these interactions is crucial for accurate diagnosis and effective treatment strategies. This review explores the epidemiology, pathology, immune response modulation, and clinical outcomes of respiratory viral coinfections, emphasizing the importance of experimental models in elucidating the dynamics of these infections. Respiratory viral coinfections are common, with approximately 10–20% of all respiratory infections involving multiple viruses. Studies show that coinfections can alter disease outcomes, with some cases leading to more severe symptoms and increased hospitalization rates. Common coinfection combinations include influenza A virus (IAV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), rhinovirus (RV), human metapneumovirus (HMPV), and human parainfluenza virus (HPIV). The prevalence of these coinfections varies by region, season, and demographic factors, highlighting the need for comprehensive surveillance and targeted prevention strategies. The immune response to respiratory viral coinfections is complex, with interactions between viruses influencing cytokine production and immune cell activation. Some viruses can enhance the replication of others, while others may inhibit viral replication or modulate immune responses. Experimental models, such as mice, hamsters, and ferrets, are essential for studying these interactions, as well as in vitro models like air-liquid interface cultures and lung organoids. These models help researchers understand the pathogenesis and immune modulation associated with coinfections. Future research should focus on improving diagnostic methods, understanding the mechanisms of viral interactions, and developing targeted interventions to mitigate the severity of respiratory viral coinfections. Advances in genomic surveillance and mathematical modeling can further enhance our understanding of these complex interactions, leading to more effective prevention and treatment strategies.