Viral lower respiratory tract infection (LRTI) can lead to severe disease at all ages, but with the exception of influenza vaccination, prevention is not available for most respiratory viruses, hence, effective, disease-limiting therapy is urgently required. To enable the development of novel effective therapeutic approaches, we need to improve understanding of the pathological mechanisms of viral LRTI. Here, we will discuss recently gained new insight into early, innate immune and inflammatory responses to respiratory viruses by airway epithelial cells and mucosal immune cells. Following virus recognition, these cells generate a range of mediators, including innate interferons, proinflammatory cytokines, and growth and differentiation factors which have pivotal roles in effective virus control, and the development of inflammation and disease in viral LRTI.