While the best-known role of B cells is the central player of “humoral immunity”, B cells also modulate immune responses through antigen presentation and cytokine secretion. Indeed, B cell-targeted therapy including monoclonal antibodies to CD20, CD22, and BAFF are considered as a promising strategy to various inflammatory/autoimmune diseases. By contrast, “regulatory B cells” that suppress immune responses have also been recognized as an important new component of the immune system. For example, contact hypersensitivity (CHS) has been considered as a prototypic form of delayed-type hypersensitivity, a classic T cell–mediated inflammatory reaction where B cells and antibodies are not involved in the process. However, unexpectedly, recent studies revealed that B cells also have a critical inhibitory function in this response. Regulatory B cells also exert potent inhibitory functions in autoimmune diseases such as lupus. In this talk, recent findings regarding the biology of regulatory B cells and their role in allergic and autoimmune diseases from my laboratory and others will be discussed. Clarifying the molecular mechanisms by which regulatory B cells suppress immune responses in these diseases will be of great benefit in developing the next generation of B cell-targeted therapeutic strategies.