Aging is associated with an alteration of the immune response called immunosenescence. It is now well accepted that all parts of the immune system, the adaptive as well as the innate, undergo immunosenescence. However, the adaptive immune response and especially T cell functions are the most affected by aging. Aging is associated with profound changes in lymphocytes subpopulations, however, the functional changes within these subsets are more important to elucidate. Indeed, T cells present functional modifications resulting in a decreased clonal expansion and interleukin-2 (IL-2) production. So there should be an alteration in the activation process of T cells with aging involving the T cell receptor (TCR) and CD28 receptor signaling cascades. The alterations in membrane rafts composition and function can underline this altered activation of T cells with aging and then contribute to human immunosenescence. The experimental data in favor of this hypothesis will be reviewed.