Background: Emerging respiratory diseases can spread rapidly within closely tied, immune-naive populations through respiratory droplets and aerosols. Many have non-specific symptoms making them especially difficult to identify, differentiate and treat quickly and appropriately. Others have re-emerged as a result of changes in vaccine production and availability. Increased international trade of animals can also impact disease dynamics, making it easier for zoonotic respiratory viruses to spread to new populations. Methods: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance data was collected among three US populations from 2011 to 2013 to evaluate clinical predictors of pathogen specific respiratory disease, seasonality and co-infection rates. Similarly, FRI surveillance at eight US military recruit training centers from 1996 to 2013 was used to assess the impact of adenovirus vaccines on respiratory disease rates. Finally, a retrospective analysis evaluated the risk of poultry avian influenza (H5N1) infection in an importing country based on the quantity of birds traded, infection in the exporting country, and their statistical interaction. Results: In the first study, clinical and demographic predictors of rhinovirus, influenza, other pathogen, and no/unknown pathogen were identified. The second study found that military trainees experienced a 100-fold decline in adenovirus disease burden during the two years after adenovirus vaccines reintroduction. Results from the third study suggest that risk of H5N1 poultry infection in an importing country increased by a factor of 1.3 (95% CI: 1.1-1.5) for every 10-fold increase in live chickens imported from countries experiencing at least one case during that year. Conclusions: Identifying demographic or clinical variables that are predictive of specific respiratory diseases is important for improving timely and accurate treatment, and recognizing the emergence of new pathogens or strains. For respiratory pathogens with existing vaccines, monitoring and evaluating vaccine benefit is important to ensure continued investment in vaccine production and prevent future disease reemergence. Additionally, limiting movement of infected animals by reducing chicken trade during H5N1 epidemic periods or increasing biosecurity measures can also reduce disease spread. Overall, prevention through early identification of cases, vaccination, and targeting transmission networks is important for preventing epidemics or pandemics of new respiratory infections.