Immunosenescence (ageing of the immune system) contributes to the increased susceptibility of the elderly to infectious disease, and to the poor outcome of vaccination. Longitudinal studies reveal an “immune risk profile” (IRP), independent of genetic background or state of health at baseline, which predicts mortality on follow-up in the elderly. Immunosenescence seems to be accelerated by the requirement for constant immunosurveillance against herpesviruses, especially cytomegalovirus (CMV) and to a lesser extent Epstein-Barr virus. The number of different CMV-specific CD8+ T cell clones increases with age, but then decreases in the terminal phase, accompanied by accumulation of dysfunctional CMV-specific CD8 cells in the blood. These events are associated with incipient mortality in old people. Such dysfunctional, anergic T cells already begin to accumulate in middle age, and this continues throughout life. Longitudinal studies ex vivo in the elderly, as well as the utilisation of cell cultures as in vitro models of T cell clonal behaviour under chronic antigen exposure, are essential for understanding immunosenescence and for testing interventions to achieve healthy longevity. The discovery that CMV contributes to immunosenescence suggests that prophylactic vaccination early in life or pharmacological intervention in later life might improve immunity in old age.