Deterioration of the immune system and the endocrine system during aging is thought to contribute to increased morbidity and mortality. Since bidirectional interrelations of both systems are present in the young and in the elderly, endocrinosenescence modulates the immune system and immunosenescence changes the endocrine system. This review focuses on age-related changes of the two systems and provides examples for the interaction of both systems during aging. It is demonstrated that both systems modulate each other in a probably unfavorable way which may be a cofactor in the aging process. Understanding of these bidirectional physiological mechanisms will help to define targets for therapeutical intervention to improve the health of aging people.