B-cell development is characterized by the progressive maturation of hematopoietic stem cells through several stages to ultimately give rise to the mature B-cell pool that has been selected for reactivity against non-self antigens. Thus, the mature pool of naive B cells is capable of elicting high-affinity responses following natural infection with pathogens or vaccination and provides the host with protective long-lived humoral immunity. However, perturbations during the processes of B-cell development and differentiation can give rise to a diverse array of immunological diseases including autoimmunity, immunodeficiency and malignancy. While we have a very rich understanding of the processes underlying B-cell development in mice, our knowledge of the corresponding events occurring in human B cells is substantially less robust. Here, we overview the latest findings relating to human B cells in health and disease with a particular emphasis on the transitional stage of B-cell development.