Combination therapy has emerged as a crucial therapeutic tool to control aggressive rheumatoid arthritis (RA). Cyclosporine (CsA) when combined with methotrexate (MTX) has shown substantial benefit in clinical practice. The primary benefit is its positive effect in the control of joint-bone erosions. The most feared adverse effect is the development of nephrotoxicity, which may be in part hemodynamic and in part structural, i.e. fibrotic. Careful monitoring of concomitant drugs, hypertension and through blood levels should allow the patient to maintain normal renal function. The successful employment of CsA in lupus nephritis clearly supports this statement.