From birth, the microbiota plays an essential role in human development by educating host immune responses. Proper maturation of the immune system perturbs chronic inflammation and the pathogenesis of disease by preventing inappropriate immune responses. While many have detailed the roles of specific microbial groups in immune development and human disease, it remains to be elucidated how the microbiota influences the immune system during aging. Furthermore, it is not yet understood how age-related changes to the microbiota and immune system influence the development of age-related diseases. In this review, we outline the role of the microbiota in immune system development as well as functional changes that occur to immune cell populations during immunosenescence. In addition, we highlight how commensal microbes influence the pathogenesis of cancer, a prominent disease of aging. The information provided herein suggests that age-related changes to the microbiota and immune system should be considered in disease treatment and prevention strategies.