Normal immune functions can begin to decline shortly after an individual reaches sexual maturity. Although changes in cellular environment are partially responsible, the decline is due primarily to changes within the cells, especially the T cells and to some extent the stem cells. This is reflected in their inability to proliferate and differentiate efficiently. What needs to be resolved is whether the altered properties of T cells and stem cells are permanent or reversible and, if permanent, whether they are due to a stochastic or genetically programmed event. The decline with age in certain normal immune functions is associated with an increase in the frequency of autoimmune and immune complex diseases, certain types of cancer, and viral and fungal infections. These diseases, compromise normal immune functions in short-lived strains of mice. In long-lived mice and in humans, however, the decline in immune functions to threshold levels seems to predispose in individuals to illness.