Managing chronic inflammatory immune-mediated eye diseases currently involves the non-specific suppression of the immune system. Oral corticosteroids are still the chief component of this therapy, but additional immunosuppressive agents are often indicated to control the disease as well as to avoid the side effects of long-term therapy with high doses of corticosteroids. Many different drugs are available including cyclosporine, azathioprine and occasionally cyclophosphamide, chlorambucil, or more recently mycophenolate mofetil and tacrolimus (FK-506). Pulsed low-dose oral methotrexate (MTX) is now widely used in rheumatological disease and has been introduced in the management of sight-threatening uveitis. Some reports using low doses advocate its use as an alternative when multiple drug therapy is necessary or to help lower the dose of other drugs. In our group of 11 patients with long-standing disease, adding MTX to the treatment regimen allowed control of the inflammation with a reduction of the corticosteroid dose in more than 50% of the cases and decreased the number of disease relapses in 45%. These results indicate that MTX is useful as an alternative option when a second/third agent is needed, achieving a better control of the disease in some cases.