B cells are essential for Ab production during humoral immune responses. From decades of B cell research, there is now a detailed understanding of B cell subsets, development, functions, and most importantly, signaling pathways. The complicated pathways in B cells and their interactions with each other are stage-dependent, varying with surface marker expression during B cell development. With the increasing understanding of B cell development and signaling pathways, the mechanisms underlying B cell related diseases are being unraveled as well, making it possible to provide more precise and effective treatments. In this review, we describe several essential and recently discovered signaling pathways in B cell development and take a look at newly developed therapeutic strategies targeted at B cell signaling.