Cyclophosphamide has been widely studied for the treatment of MS and the effective stabilization of selected patients on therapy has been suggested in several studies. This drug has selective effects on the immune response, such as suppression of helper Th1 activity and enhancement of helper Th2 responses; both of these processes are thought to be involved in the beneficial effect of cyclophosphamide in MS. Over the years, especially with the advent of magnetic resonance imaging (MRI), there has been an improved understanding of the profound anti-inflammatory effect of cyclophosphamide, evidenced by its effect on clinical relapses and contrast-enhancing lesions on MRI. Toxic effects on the bladder and the risk of malignancy prevent the widespread use of cyclophosphamide in early MS; however, it can be dosed safely and is usually well tolerated in actively progressing relapsing-remitting or early secondary progressive MS cases that are unresponsive to beta interferon and glatiramer acetate.