The lack of sensitivity of rapid immunoassays in detecting the novel 2009 H1N1 influenza virus infection has led to recommendations on influenza diagnostic testing for clinicians treating patients as well as advising clinicians on testing decisions. Studies have also shown that rapid immunoassays for seasonal influenza virus show considerable variability in performance characteristics, based on age of patient, prevalence of disease, course of infection, and the quality of the kit used. While public health authorities are currently focused on influenza virus diagnostics, a lack of sensitivity of rapid immunoassays for other viral respiratory pathogens has been widely reported, such as the very limited value of rapid immunoassays for the detection of respiratory syncytial virus in adults. In light of the lack of sensitivity of diagnostic tests for suspected 2009 H1N1 influenza virus infection, as well as their variable performance characteristics for seasonal influenza virus, a number of recommendations have been made by public health authorities advising clinicians on the need for clinical judgment as an important part of testing and treatment decisions as well as reliance on local epidemiologic and surveillance data. With the availability of new molecular methodologies that are user-friendly and allow the front-line physician as well as hospital infection control programs to significantly improve respiratory viral diagnostics, there is a need to carefully determine the most optimal diagnostic testing methodology based on the clinical setting. This review will describe the historical, current, and changing dynamics of respiratory virus infection diagnostics.