Recent advances in our understanding of cellular and molecular mechanisms of rheumatoid arthritis have highlighted a critical role for interleukin-1 and tumor necrosis factor alpha. The quest for chemically amenable targets has recently led to the identification and characterization of the intracellular signaling pathways associated with these inflammatory cytokines. In particular the mitogen-activated protein kinase pathway, the nuclear factor kappaB pathway and the cross-talk between these offer several potential therapeutic opportunities for rheumatoid arthritis.