© 2003 Elsevier Ltd. All rights reserved. This chapter discusses the development and function of B cell subsets. Precursor B cells differentiate int B-lymphocytes after expressing a functional surface immunoglobulin receptor (sIgM). These newly formed B cells are then subject to further selection steps during their entry in the mature, long-lived pool of peripheral B-lymphocytes. Phenotypic, topographic, and functional characteristics have been used to delineate subsets of mature B-lymphocytes. Based on such criteria, these subsets have been shown to have different developmental programs as well as generation and maintenance requirements. The most prevalent of these subsets is the mature B2 cell population, which is also heterogeneous. B1 B cells are self-renewing cells with cell cycle and activation properties, different from the bulk of recirculating B2 cells. These predominate in the peritoneal and pleural cavities. Marginal zone (MZ) B and B1 cells are characterized by their ability to respond early and rapidly in immune responses. B cell subsets being functionally different have preferences for particular niches in the immune system. The compartmentalization of each of these B cell subsets is suggestive of specialized functions linked to the niches within the spleen in which they reside. This chapter closes with future research that will be directed at the elucidation of clonal signals and co-signals and the miroenvironments, within which B cell subsets receive these developmental guides. Knowledge of the chemokines and adhesion molecules that are involved in the direction of and retention of B cells within these microenvironments will be forthcoming.