© 2003 Elsevier Ltd. All rights reserved. This chapter discusses the development of B-lymphocytes. B lineage cells in humans are progeny of the lymphoid progenitors that derive from multi-potential hematopoietic stem cells. Their orchestrated development begins in lympho-hematopoietic sites in the fetal liver and then continues in the bone marrow throughout life. The chapter describes the genotypic and phenotypic features that mark the progression of the cells along the developmental pathway, noting significant species differences in the process and indicating where human mutations have provided important clues to the gene function. It outlines the progression of the V(D)J gene rearrangements required for the expression of immunoglobulin (Ig), the antigen receptor and effector molecule of the B lineage, and describes the contribution of the secondary V(D)J rearrangements to the human B cell repertoire The chapter closes with an overview of two important types of abnormal human B cell development, the primary immunodeficiency diseases and the acute lymphoblastic leukemia of B lineage.