The Src-family protein tyrosine kinases (SFKs) are known to play key roles in initiating signal transduction by the B-cell antigen receptor (BCR). In addition, numerous studies have shown that this family of molecules also contributes to signaling by BCR surrogates during B-lymphocyte lineage development and maturation. Paradoxically, ablation of SFKs not only results in obvious defects in B-cell development but also in the onset of autoimmunity. Thus SFKs, most notably Lyn, play both activating and inhibitory roles in B-cell function. Confounding analyses of SFK function in B cells is the varied coexpression of family members that mediate redundant as well as unique functions. In this review, we will focus mainly on the role of Lyn in mediating positive and negative roles in B-cell activation and how these affect immune signaling and disease progression.