The ability of B cells to stimulate T cell–mediated immune responses through antigen presentation, co–stimulation and cytokine production has attracted great attention due to its significance for therapeutic intervention in inflammatory and autoimmune disorders. Nowadays, observations from a number of experimental approaches as well as in patients with inflammatory and autoimmune diseases have equally emphasized a significant function for B cells in maintaining immune homeostasis through maintenance of tolerance and prevention of unrestrained inflammation. Whereas studies by many investigators have started to identify the key mechanisms and molecules that support these processes, further effort is necessary to comprehend the diversity of regulatory B cell subsets and the cues that prompt their fate as regulatory versus proinflammatory. In this review I summarize the latest knowledge on the phenotypic and functional characteristics of different regulatory B cell populations, the cues that orchestrate their induction, and their potential therapeutic relevance.