B cells have emerged as important immune cells in cardiovascular disease. Initial studies have suggested that B cells protect against atherosclerosis development. However, subsequent studies demonstrating aggravation of atherosclerosis by B-2 cells have shed light on the subset-dependent effects of B cells. Here, we review the literature that has led to our current understanding of B cell regulation of atherosclerosis, touching on the importance of subsets, local regulation, human translation, and therapeutic potential.