The expression of lineage-associated genes, as well as the survival and expansion of committed B cell progenitors, is controlled by multiple transcriptional regulators and growth-factor receptors. Whereas certain DNA-binding proteins, such as Ikaros and PU.1, are required primarily for the formation of more primitive lymphoid progenitors, other factors such as E2A and EBF1 have more direct roles in specifying the B cell-specific gene-expression program. Further, Pax5 functions to promote B cell commitment by repressing lineage-inappropriate gene expression and reinforcing B cell-specific gene expression. In this review, we focus on recent studies that have revealed that instead of a simple transcriptional hierarchy, efficient B cell commitment and differentiation requires the combinatorial activity of multiple transcription factors in a complex gene regulatory network.