Vaccination is considered the most effective means of reducing influenza burden, providing substantial benefits in terms of reduction of morbidity, complications, hospitalizations and deaths, even if vaccines have been associated with a reduced immune response and lower effectiveness in older adults, in particular when a mismatch between the vaccine and the circulating virus strains occurred. Several strategies have been proposed to enhance vaccine protection against drifted strains, including the use of adjuvants. Among oil-emulsion adjuvants, MF-59 was approved for human use more than a decade ago and it is largely used for adjuvantation of influenza vaccine. Recent studies have demonstrated that addition of the MF-59 to subunit influenza vaccine can lead to higher haemagglutination-inhibiting seroprotection rates and to higher neutralization antibody titers against drifted strains not included in the vaccine respect to non-adjuvanted vaccine. Promising results were obtained using a new generation of oil-in-water emulsion adjuvants, named AS, offering cross-protection against heterologous challenge in ferrets.