The emergence of influenza A/H5N1 viruses in Asia has raised concerns about their potential to cause pandemic disease. Because vaccination is the primary strategy for the prevention of influenza, efforts are in progress to develop safe and immunogenic vaccines against these viruses and other potential pandemic influenza strains. Results of initial studies indicated that subunit influenza A/H5N1virus vaccines were poorly immunogenic, and that high dosages were needed to induce seroresponses in the majority of subjects. Addition of aluminum-containing adjuvants resulted in variable effects on the immunogenicity of H5 vaccines, but in general, clinically meaningful effects have not been observed. Intradermal immunization was not associated with significant enhancement in one study. More recent studies indicate that oil-in-water adjuvants significantly enhance immune responses when compared with nonadjuvanted preparations containing the same dosage of H5 or H9 hemagglutinin. In addition, these formulations elicit higher levels of cross-reactive antibodies vs. different H5N1 clades. Several whole-virus vaccines have been demonstrated to stimulate high frequencies of responses at relatively low dosages; however, direct comparisons with subunit vaccines have not been made. Finally, candidate live attenuated vaccines are under evaluation in clinical trials. The results of these and future trials will help to identify formulations and immunization regimens for various populations, and will better prepare us to address the threat of both pandemic and interpandemic influenza.