Aging is associated with declines in immune system function, or 'immunosenescence', leading to progressive deterioration in both innate and adaptive immunity. These changes contribute to the decreased response to vaccines seen in many older adults, and morbidity and mortality from infection. Infections (e.g., influenza, pneumonia and septicemia) appear among the top ten most-common causes of death in adults in the USA aged 55 years and older. As immunosenescence has gathered more attention in the scientific and healthcare communities, investigators have demonstrated more links between immunosenescent changes and morbidity and mortality related to infections and declining vaccine responses. This review summarizes the recent literature on age-dependent defects in adaptive and innate immunity, data linking these defects to poor vaccine response and morbidity and mortality, current recommendations for vaccinations and potential strategies to improve vaccine efficacy in older adults.