The spread and evolution of highly pathogenic influenza A/H5N1 viruses in birds worldwide, and the associated human fatalities, have raised concern about an imminent influenza pandemic. Studies evaluating the safety and immunogenicity of traditional (egg-grown, subvirion and whole virus) vaccines and alternative vaccine approaches (recombinant, live-attenuated and adjuvanted vaccines) have been performed. Results show that, using unadjuvanted subvirion vaccines, at least two vaccine doses containing high dosages of influenza virus hemagglutinin are needed to elicit a titer of antibody that has been associated with protection in vaccinated subjects. High antigen-dosage requirements may be reduced and immunogenicity improved with the use of whole virus vaccines or adjuvants, such as MF59 and GlaxoSmithKline proprietary adjuvant. There is a suggestion that prepandemic priming against drifted H5N1 variants is possible; however, additional data are needed. Newer approaches using live-attenuated, DNA vaccines and conserved epitopes are currently under development.