An important role for cytokines, particularly tumor necrosis factor (TNF) and interleukin-1 (IL-1), in the pathogenesis of rheumatoid arthritis (RA) is now well established (1, 2). The dramatic clinical success of treatment with TNF and IL-1 blockade has led to substantial interest in understanding the regulation of TNF and IL-1 production and in therapeutic targeting of signaling pathways and transcription factors utilized by TNF and IL-1. This includes mitogen-activated protein kinase cascades and other pathways that lead to the TNF-and IL-1–induced activation of nuclear factor B and activator protein 1 (3–7). The janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway has received less attention among RA researchers. However, several cytokines implicated in RA pathogenesis, including IL-6, IL-15, granulocyte–macrophage colony-stimulating factor, and interferons (IFNs), activate the JAK/STAT pathway, and STAT-3 is constitutively activated in RA (8). Treatment of RA with an anti–IL-6 antibody that is predicted to block JAK/STAT activation appears promising (9). Thus, it is important to evaluate the role of JAKs and STATs in RA pathogenesis and to determine whether these molecules are good therapeutic targets. An important step in this direction has been taken by van der Pouw Kraan and colleagues, who report in this issue of Arthritis & Rheumatism that STAT-1 target genes are expressed in RA synovium (10), thus providing evidence for an active role for this transcription factor in the disease process.