The standard in vitro assays used for the generation and characterization of antibodies that bind and neutralize the influenza virus have not been modified significantly in many years. The use of cultured human cells has been instrumental in understanding the basis of the immune response, and the in vitro generation of influenza-specific antibodies may be used to provide novel insights into the selection of potential vaccines. Furthermore, the essential functional assays that evaluate the antibody response have several features that could be improved, including increased sensitivity, the ability to use an inactivated virus, the automation and mechanization of analytic readouts, and inter-laboratory consistency. This feature review discusses a series of assays that have been developed to address these issues and improve the ability to evaluate the anti-influenza antibody response.