Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysfunction may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. Mounting biological evidence supports the potential clinical relevance and impact of immunosenenscence. We briefly review immunosenescence with a focus on replicative senescence in cytotoxic T cells and recent clinical studies examining its association with influenza and infectious disease outcomes.