Primary Sjögren’s syndrome was long a vexing dilemma, as the underlying pathophysiological mechanisms remained obscure, disease activity was challenging to evaluate, and no specific treatments were known to be effective. However, recent years have witnessed major advances in these three areas. Convincing evidence has been obtained that innate immunity, most notably mediated by the interferons, plays a role in the initial B-cell activation. A disease activity score was developed during a consensus conference sponsored by the EULAR. Even more importantly, B-cell depletion constitutes a highly promising therapeutic approach. Thus, rituximab was effective in two controlled clinical trials.