B lymphocytes are often essential to successfully control invading pathogens and play a primary role in the protection afforded by successful vaccines through the production of specific antibodies. However, recent studies have highlighted the complex roles of B cells in infectious diseases, showing unexpectedly that some activated B cells limited host defense towards pathogens. This B-cell function involves production of regulatory cytokines including IL-10 and IL-35 and is reminiscent of the regulatory functions of B cells initially defined in autoimmune diseases. It is now known that various types of microbes including bacteria, helminths and viruses can induce IL-10-expressing B cells with inhibitory functions, indicating that this response is a general component of anti-microbial immunity. Interestingly, IL-10-producing B cells induced in the course of some microbial infections can inhibit concurrent immune responses directed towards unrelated antigens in a bystander manner and as a consequence ameliorate the course of autoimmune or allergic diseases. This could explain how some micro-organisms might provide protection from these pathologies, as formulated in the ‘hygiene hypothesis’. In this review, we discuss the regulatory functions of B cells in bacterial, parasitic and viral infections, taking into account the phenotype of the B cells implicated, the signals controlling their induction and the cell types targeted by their suppressive activities.