Toll-like receptors (TLRs) and their ligands have emerged as important regulators of immunity, relevant to a wide range of effector responses from vaccination to autoimmunity. The most well-studied ligands of TLRs expressed on B cells include the lipopolysaccharides (for TLR4) and CpG-containing DNAs (for TLR9), which induce and/or co-stimulate B cells to undergo proliferation, class switching and differentiation into antibody-secreting cells. Recent developments in this area include advancements into our understanding of the role of these receptor pathways in B cells, and in particular the relevance of TLR9, which has received substantial attention as both a Th1-like inflammatory immunomodulator and a pathogenic co-stimulator of autoreactive B cell responses.