The decreased efficiency of immune responses in older people is partly a consequence of alterations in T lymphocyte functions caused by modifications in the early events of signal transduction. Several alterations in the signaling pathways of T lymphocytes have been described in older humans and animals. A unifying cause could be modifications in the physicochemical properties of the plasma membrane resulting from changes in its lipid composition and the distribution and function of lipid rafts (LR). The latter serve to assemble the initial components of the signaling cascade. Accumulating data suggest that the function of plasma membrane LR is altered with aging; we hypothesize that this would significantly contribute to immune dysregulation. The role of aging and cholesterol in LR functions in T lymphocytes is reviewed and discussed here.