The introduction of biologic agents represented an important advance for the treatment of RA. These agents are efficacious options for patients no responder to, or intolerant of conventional DMARDs allowing not only to improve signs and symptoms of the disease but also to prevent joint damage and future disease severity. They target specifi c immunological pathways that have been demonstrated being crucial in the pathogenesis of the disease. Biologics can be divided into 3 categories on the basis of their structure: soluble receptors, monoclonal antibodies and receptor antagonists. Soluble receptors are fusion proteins that combine the ligand binding regions of receptors normally found on the cells’ surface with an immunoglobulin Fc region. Once a cytokine is bound to the soluble receptor, this link prevents it from binding the normal receptor on the cell. Monoclonal antibodies can bind to cytokines in the circulation or to proteins present on the cell surface and once bound, this linkage clears the cytokine from the circulation and prevents its linkage to the target receptor. Moreover, monoclonal antibodies directed against specifi c proteins on the cell surface can deplete those cells either through apoptosis, complement mediated cell lysis or Fc receptor mediated clearance. Finally the receptor antagonist can mimic the function of native proteins and is able to occupy a cell-surface receptor preventing the engagement and the binding by its specifi c natural ligand.