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The Spleen Tyrosine Kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is an important mediator of immunoreceptor signaling in macrophages, neutrophils, mast cells and B-cells. Based on the anti-infl ammatory activity detected in collagen induced arthritis models and in human synoviocytes cultures, the Syk inhibitor fostamatinib disodium (R788) (that is a prodrug that after oral administration is converted into its active metabolite R406) was tested on RA patients in a Phase II trial (Weinblatt et al. 2008) showing a signifi cant clinical benefi t (at the dose of 100 mg and 150 mg) in a population of patients with active RA receiving methotrexate therapy at 12 weeks. More recently, fostamatinib has been tested in RA patients who failed biologics (Genovese et al. 2010) showing no signifi cant differences the ACR responses at 3 months compared to placebo.