B lymphocytes and T lymphocytes develop from hematopoietic stem cells through a series of intermediates with progressively decreased lineage differentiation potential. Differentiation is preceded by increased accessibility of the chromatin at genes that are poised for expression in the progeny of a multipotent cell. During the process of differentiation there is increased expression of lineage-associated genes and repression of lineage-inappropriate genes resulting in commitment to differentiation through a specific lineage. These transcriptional events are coordinated by networks of transcription factors and their associated chromatin remodeling factors. The B lymphocyte lineage provides a paradigm for how these events unfold to promote specification and commitment to a single developmental pathway.