The molecules that regulate bone cell development, particularly at the early stages of development, are only partially known. Data are accumulating that indicate a complex relationship exists between B cells and bone cell differentiation. Although the exact nature of this relationship is still evolving, it takes at least two forms. First, factors that regulate B‐cell growth and development have striking effects on osteoclast and osteoblast lineage cells. Similarly, factors that regulate bone cell development influence B‐cell maturation. Second, a series of transcription factors required for B‐cell differentiation have been identified, and these factors function in a developmentally ordered circuit. These transcription factors have unpredicted, pronounced, and non‐overlapping effects on osteoblast and/or osteoclast development. These data indicate that at least a regulatory relationship exists between B lymphopoiesis, osteoclastogenesis, and osteoblastogenesis.