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Rheumatoid arthritis (RA) are chronic, inflammatory autoimmune diseases potentially leading to functional disability, deterioration in patients health-related quality of life and life expectancy, Drug resistance is also accepted as an important cause of treatment failure for patients with autoimmune disease.ATP binding cassette (ABC) proteins are widely expressed in cell types relevant to pathogenesis of RA.Molecular mechanisms underlying drug resistance include the action of drug efflux pumps belonging to the super-family of ATP binding cassette (ABC) proteins, which mediate the cellular extrusion of a large variety of therapeutic drugs(e.g.methotrexate, sulfasalazine, leflunomide/teriflunomide, hydroxychloroquine), a phenotype that is referred to as multidrug resistance (MDR).Consequently, the activity of this transporter in patients should be determined to understand the disposition and pharmacokinetics of the therapy.Further more, MDR-ABC transporters transport a variety of endobiotics that play important roles in cell proliferation, cell migration, angiogenesis and inflammation.Therefore, MDR-ABC transporters are important biomarkers in rheumatoid arthritis.Based on knowledge from the field of oncology and immunology, this review concentrates on the pharmacological role of MDR proteins in the (clinical) efficacy of several disease modifying antirheumatic drug, as well as the physiological role of MDR proteins in transporting signalling molecules important in inflammatory processes.