Atherosclerosis is a leading cause of death worldwide. It is a complex chronic inflammatory disease involving interactions between vascular, circulating and immune cells. B cells play an important role in chronic inflammation producing antibodies and regulating T and natural killer (NKT) cell activation. The role of B cells in atherosclerosis is complex, with atherogenic and protective roles assigned for distinct B cell subsets. Drugs that deplete B cells or modulate their functions are now used in the treatment of various autoimmune diseases in humans. Here, we briefly review the roles of B cell subsets in atherogenesis, and emphasize the potential impact of B cell targeted therapies on the cardiovascular risk of treated patients. Developing more B cell subset-specific therapies would lead to more effective treatments with enhanced safety profile.