Many fundamental concepts about immune system development have changed substantially in the past few years, and rapid advances with animal models are presenting prospects for further discovery. However, continued progress requires a clearer understanding of the relationships between haematopoietic stem cells and the progenitors that replenish each type of lymphocyte pool. Blood-cell formation has traditionally been described in terms of discrete developmental branch points, and a single route is given for each major cell type. As we discuss in this Review, recent findings suggest that the process of B-cell formation is much more dynamic. © 2008 Nature Publishing Group.