Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elderly. Of note is the higher production of peripheral T-regulatory cells.The frequent development of autoimmunity in the elderly was suggested to take place in part due to the selection of T cells with increased affinity to self-antigens or to latent viruses. These cells were shown to have a greater ability to be pro-inflammatory, thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output decreases in association with the loss of thymic capacity to generate new T cells. However, to balance the above mentioned autoimmunity and prevent the development of autoimmune diseases, there is an age-related increase in peripheral CD4+ CD25highFoxP3+ T-regulatory cells. It remains unclear whether this is an age-related immune dysfunction or a defense response. Whatever the reason, the expansion of T-regulatory cells requires payment in terms of an increased incidence of cancer and higher susceptibility to infections.