Pulmonary viral infections are associated with substantial morbidity and socioeconomic costs. Rhinovirus, influenza A and B, adenovirus, parainfluenza, respiratory syncytial virus (RSV), and coronavirus are etiologies most often associated with infections of the upper and lower respiratory tract. Therapy of viral infections in nonimmunocompromised hosts has only developed slowly during recent years, despite the enormous socioeconomic impact. This is in part due to the complex virus/host interactions and numerous and varying mechanisms of infection. Neuraminidase inhibitors have produced notable progress in the therapeutic approaches to influenza-associated pulmonary infections and are at least able to shorten the duration of symptoms in selected patients. However, neuraminidase inhibitors can only be applied in specific infections and the spectrum of agents with antiviral activity is broad. This article summarizes major principles of antiviral efficacy and reviews recent clinical trials.