Pharmacotherapy is still the cornerstone in the management of rheumatoid arthritis (RA). Due to several reasons the pharmacotherapeutic strategy has changed dramatically in the past decades. It has become clear that in most cases single treatment with disease modifying antirheumatic drugs (DMARDs) is insufficient to control the disease on the long term. This is the main reason why combinations of second-line agents are increasingly being used in the treatment of established RA. Many different ways of prescribing combination treatment and a large number of different combinations have been published. However definite conclusions which drugs to combine or what strategy to apply are difficult to make as solid studies which enable these conclusions are sparse. Several studies have shown that the best opportunity to achieve a good response is to use a set-up approach, in addition different studies have shown that corticosteroids do have a profound effect on disease activity variables.