Most patients do not exhibit overt signs of immunosuppression. Studies cited in this article support a modest increase in the rate of bacterial respiratory and skin infections. Opportunistic infections occur rarely, however, and may be life threatening. The case for MTX carcinogenicity is less clear. The risk for malignancy other than lymphoproliferative disorders does not seem to be elevated, although multiple sporadic malignancies have been reported in treated patients. MTX is a superb agent for the therapy of a large group of immune-mediated diseases. Although an increased risk for infection and possible malignancy exists, the risk is small compared with the potential clinical benefit.