Rheumatoid arthritis is a chronic infl ammatory disease for which an early aggressive treatment is associated with improved disease control, slower radiological progression and improved functional outcomes. To date, the therapeutical armamentarium to treat the disease includes new and highly effective DMARDs that have continued to emerge until the most recent years. Among those, biological agents targeting different infl ammatory molecules (TNF-α and IL-6) or immune cells (T and B cells) have been demonstrated to be very effective and then included in the therapeutic fl ow-chart. However, not all patients respond positively to these agents underlying the existence of different infl ammatory pathways driving the pathologic process. Moreover, several prognostic factors have been identifi ed being associated with the therapeutical response to different biological agents.