Recent studies suggest that strains of influenza A virus can spread through human populations because they form a neutral network of virus genotypes that share the same phenotype. 55, 56 Essentially, this network allows the virus to drift through neutral space connected via mutation, until a single mutation shifts to a different serotype ͑Fig. 3͒. This shift then facilitates escape from host immunity, and fosters the ability for the virus to infect a new class of susceptible hosts. Although these studies make no explicit mention of the role of such genetic robustness in flu epidemics, 55,56 the available evidence strongly suggests that the phenomenon is relevant in this case of influenza strain H3N2. Genetic robustness in the hemagglutinin ͑HA͒ gene of strain H3N2 allows the virus to drift through neutral genotypic space without a change in phenotype until it reaches a rapid saltational phenotypic shift that permits the ability for strains derived from this virus to reemerge in humans. This model is compatible with other robustness-evolvability links outlined in the literature. 57, 7, 8 Judging from phylogenetic and molecular evolution analyses of clinical isolates, it appears that the HA gene of influenza A virus appears to be under strong selection by the human immune system, 58 and perhaps this has been true for much of the evolutionary history of flu disease in humans.