Today up to 40% of Crohn's disease patients receive a concomitant therapy of TNF blockers in combination with thiopurines or methotrexate. Although data of prospective controlled trails are rare, some recently published studies indicate a more rapid onset of remission and increased mucosal healing following concomitant therapy in short term. However, data confirming the need or benefit of concomitant immunosuppressive therapy once remission has been reached remains unknown. Concomitant therapy lowers TNF-alpha induced immunogenicity, but the question of whether ATI formation also lowers the efficiency of TNF-alpha antagonists has not yet been answered to a level that would justify the use of concomitant immunosuppression. Knowing that immunosuppression increases the risk for opportunistic infections and lymphomas the potential risks and of concomitant therapy must be well balanced against the benefit. This article aims to interpret the available data on the efficiency, immunogenicity, and safety of concomitant therapy in patients under anti-TNF therapy.