Studies of normal blood cell development and malignant transformation of hematopoietic cells have shown that the correctly regulated expression of stage- and lineage-specific genes is a key issue in hematopoiesis. Experiments in transgenic mice have defined a number of transcription factors such as SCL/Tal, core-binding factor/acute myeloid leukemia, and c-myb, all crucial for the establishment of definitive hematopoiesis and development of all blood cell lineages. Other regulators such as IKAROS, E47/E2A, early B cell factor, Sox-4, and B cell-specific activator protein (Pax-5) appear crucial, more or less selectively, for B lymphopoiesis, allowing for detailed analysis of the development of this lineage. In addition, several of these transcription factors are found translocated in human tumors, often resulting in aberrant gene expression or production of modified proteins. This article concerns the role of transcription factors in B lymphoid development with special focus on lineage initiation and commitment events but also to some extent on the roles of transcription factors in human B lymphoid malignancies.