The continuous global increase in life expectancy represents a central challenge for our society and impacts public social security systems, families and individuals. One of the most striking changes that occur during normal human aging is immunosenescence, a progressive and overall diminution of immune functions that affect all cells and organs of the innate and adaptive immune system. As a hallmark of human aging, the progressive involution of the thymus leads to a disturbed balance and function of naïve, memory and effector T cells, thus promoting a latent pro-inflammatory status in the elderly. Together with chronic infections such as cytomegalovirus, that accumulate during life, this situation manifests in clinically relevant implications such as poor overall immune responses, decreased ability to control infectious disease and diminished response to vaccinations. Interestingly, this process parallels changes in the hormonal balance of aging subjects. In this review, we summarize recently published intriguing results from a very active and growing field of biomedical research and discuss some clinical consequences as well as possible ways of immune- and/or hormone-based interventions to delay or reverse immunosenescence.