Periodontitis and rheumatoid arthritis (RA) are common chronic inflammatory conditions and share many clinical and pathologic features. There is evidence to suggest that similar profiles of cytokine genotypes and their coding proteins are involved in the pathogenesis of periodontitis and RA. In particular, constitutive overproduction of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), has been implicated to play a pathologic role in the two inflammatory diseases. Results from studies with animal and human subjects have suggested an improvement of periodontal inflammatory condition after treatment with TNF-α inhibitors. Likewise, IL-6 receptor inhibition therapy has been suggested to have an effect on control of periodontal inflammation in patients with RA. In the present review, we provide an overview of studies showing the pathological role of cytokines in the linkage between periodontitis and RA, and further summarize the current studies assessing the effect of cytokine targeted therapy on periodontal condition.