Influenza A (H5N1) viruses are strong candidates for causing the next influenza pandemic if they acquire the ability for efficient human-to-human transmission. A major public health goal is to make efficacious vaccines against these viruses by using novel approaches, including cell-culture system, reverse genetics, and adjuvant development. Important consideration for the strategy includes preparation of vaccines from a currently circulating strain to induce broad-spectrum immunity toward newly emerged human H5 strains. This strategy would be a good solution early in a pandemic until an antigenically matched and approved vaccine is produced. The concept of therapeutic vaccines (e.g., antidisease vaccine) directed at diminishing the cytokine storm frequently seen in subtype H5N1-infected persons is underscored. Better understanding of host-virus interaction is essential to identify tools to produce effective vaccines against influenza (H5N1).