B cells positively regulate immune responses through antibody production and optimal CD4(+) T cell activation. However, a specific and functionally important subset of B cells can also negatively regulate immune responses in mouse autoimmunity and inflammation models. The lack or loss of regulatory B cells has been demonstrated by exacerbated symptoms in experimental autoimmune encephalitis, chronic colitis, contact hypersensitivity, collagen-induced arthritis, and non-obese diabetic mouse models. We have recently found that IL-10-producing regulatory B cells predominantly localize within a rare CD1d(hi)CD5(+) B cell subset that shares cell surface markers with both B-1 and marginal zone B cells. We have labeled this specific subset of regulatory B cells as B10 cells to highlight that these rare CD1d(hi)CD5(+) B cells only produce IL-10 and are responsible for most IL-10 production by B cells, and to distinguish them from other regulatory B cell subsets that may also exist. This review focuses on the recent progress in this field and the exciting opportunities for understanding how this unique B cell subset influences diverse immune functions.