Since the identification of B cells in 1965 (Cooper et al. 1965), three has been tremendous progress in our understanding of B cell development, maturation and function. A number of B cell subpopulations, including B-1, B-2 and regulatory B cells, have been identified. B-1 cells mainly originate from the fetal liver and contain B-1a and B-1b subsets. B-2 cells are derived from the bone marrow (BM) and can be further classified into follicular B (FOB) and marginal zone B (MZB) cells. Regulatory B cells (Bregs) function to suppress immune responses, primarily by production of the anti-inflammatory cytokine IL-10. B cell tolerance is established at several checkpoints, during B cell development in the BM (central tolerance) as well as during B cell maturation and activation in the periphery (peripheral tolerance). This chapter will focus on the regulation of important processes during the development and maturation of B-1 and B-2 cells.