In this review we will focus on the role of P-gp expression/function in the development of drug resistance in patients affected by systemic autoimmune diseases in particular systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and will discuss how P-gp may be a therapeutical target in the control of abnormal immune response and inflammation. The gene discussed is PGP; the disease is rheumatoid arthritis.