Regulatory T cells (Tregs) are a subset of T cells which are involved in peripheral immune tolerance. Their role in autoimmune disease which occurs through a breakdown of tolerance is of particular interest in trying to ascertain the mechanism(s) of disease progression. It is hoped that by understanding the role of Tregs in autoimmunity a reliable therapy may be developed to aid in both the treatment and potentially cure of disease. This review will focus on the naturally-occurring CD4+ CD25+ regulatory T cell subset and their possible involvement in rheumatoid arthritis.