Correlated with increasing chronologic age, immunosenescence impairs the response to influenza vaccines. MF59®-adjuvanted influenza vaccine (Fluad®, Novartis, Basel, Switzerland) elicits a stronger and broader immune response against well-matched and drifted influenza strains compared with conventional vaccines. MF5-adjuvanted influenza vaccine reduces the rate of hospitalization for pneumonia, cardiovascular disease and cerebrovascular disease, even in seasons with an imperfect match between the vaccine and circulating strains, in vaccinated compared with unvaccinated older adults.