Toll‐like receptors (TLR) play a central role in the initiation of the innate immune response to pathogens. Upon recognition of molecular motifs specific for microbial molecules TLR mediate pro‐inflammatory cytokine secretion and enhance antigen presentation; in B cells they further promote expansion, class switch recombination and immunoglobulin secretion. As a result of their adjuvant properties, TLR ligands have become an integral component of antimicrobial vaccines. In spite of this, little is known of the direct effects of TLR engagement on B‐lymphocyte function. The scope of this review is to outline the differences in TLR expression and reactivity in murine and human B‐cell subsets and to provide an overview of the currently available literature. We will further discuss the possible roles of TLR in regulating B‐cell effector functions and shaping antibody‐mediated defence against microbial pathogens in vivo.