There is an urgent need to develop novel approaches for vaccination against emerging pathogenic avian influenza viruses as a priority for pandemic preparedness. Influenza virus-like particles (VLPs) have been suggested and developed as a new generation of non-egg-based cell culture-derived vaccine candidates against influenza infection. Influenza VLPs are formed by a self-assembly process incorporating structural proteins into budding particles composed of the hemagglutinin (HA), neuraminidase (NA) and M1 proteins, and may include additional influenza proteins such as M2. Animals vaccinated with VLPs were protected from morbidity and mortality resulting from lethal influenza infections. The protective mechanism of influenza VLP vaccines was similar to that of the currently licensed influenza vaccines inducing neutralizing antibodies and hemagglutination inhibition activities. Current studies demonstrate that influenza VLP approaches can be a promising alternative approach to developing a vaccine for pandemic influenza viruses. The first human clinical trial of a recombinant pandemic-like H5N1 influenza VLP vaccine was initiated in July 2007 (Bright et al., unpublished).