B lymphocytes contribute to immunity in multiple ways, including production of antibodies, presentation of antigen to T cells, organogenesis of secondary lymphoid organs, and secretion of cytokines. Recent clinical trials have shown that depleting B cells can be highly beneficial for patients with autoimmune diseases, implicating B cells and antibodies as key drivers of pathology. However, it should be kept in mind that B cell responses and antibodies also have important regulatory roles in limiting autoimmune pathology. Here, we analyze clinical examples illustrating the potential of antibodies as treatment for immune-mediated disorders and discuss the underlying mechanisms. Furthermore, we examine the regulatory functions of activated B cells, their involvement in the termination of some experimental autoimmune diseases, and their use in cell-based therapy for such pathologies. These suppressive functions of B cells and antibodies do not only open new ways for harnessing autoimmune illnesses, but they also should be taken into account when designing new strategies for vaccination against microbes and tumors.