A number of key advantages make the immune system uniquely suited for studies of aging. The understanding of loss of immune function with aging has advanced to allow incisive evaluations of general theories of aging. Specifically, the time is ripe for examination of mechanisms leading to age-associated molecular and cellular defects in the immune system and testing of strategies to reverse identified defects. These and other opportunities are discussed in the following, with special focus upon aging of the innate immune system, the role of commensal bacteria and inflammation in immune aging, and the need for better and more precise models in mice and primates to facilitate these studies and provide translation toward clinical application of immune rejuvenation.