Janus was the Roman god of doorways and beginnings. Thus, if B-cell directed therapy is indeed the beginning of a new era in SLE therapy, his would be an appropriate face to regard in this context. But there is a problem: he is a two-faced god. Janus faces in two different directions: past and future, youth and adulthood, barbarism and civility. With respect to biological treatments, perhaps Janus' faces are the efficacy and the safety dimensions of therapy. In this review, I will consider Janus' second face, the safety side of B-cell therapy. I will argue that, while safety data have been rather reassuring so far, vigilance is required; and I will point out three specific mistaken assumptions regarding the safety of B-cell directed therapy in SLE.