Summary: Infections by intracellular bacterial pathogens remain a major cause of human diseases worldwide. Despite intensive efforts, the development of effective vaccines or immunotherapies against these diseases has largely remained unsuccessful, asking for the exploration of new aspects of the host response to these pathogens. Genetic studies have demonstrated beyond doubt that cell-mediated mechanisms of host defense involving innate immunity and T cells are of crucial importance for the control of these diseases. By contrast, the role of B cells during intracellular bacterial infection has so far received little attention besides their role as antibody-producing cells. However, the general knowledge of B-cell immunology and in particular of their antibody-independent functions has greatly increased during the last years. Recently, it was found in a model of Salmonella typhimurium infection that Toll-like receptor triggering on B cells resulted through interleukin-10 secretion in a marked suppression of innate defense mechanisms ultimately leading to uncontrolled growth of the bacteria and earlier death from the disease during both primary and secondary infections. This article reviews the protective and deleterious roles of B cells during intracellular bacterial infections and discusses how manipulating their antibody-independent functions may be a powerful means to therapeutically improve host resistance against these diseases.