The clinical course of idiopathic pulmonary fibrosis (IPF) is variable; however, the long-term survival in IPF is poor. Prednisone has been the mainstay of therapy since its release for clinical use in 1948. Recently, prednisone combined with azathioprine or cyclophosphamide has been used. A number of other drug combinations have been tried with prednisone (e.g., methotrexate, colchicine, penicillamine, or cyclosporine) but have failed or are not well tolerated by the patient. Few high quality, prospective, controlled clinical trials have been performed. Thus, there is no good evidence to support the routine use of any specific therapy in the management of IPF. Additional large clinical trials are needed to confirm the potential usefulness of the newer agents (e.g., IFN-gamma1b, pirfenidone, N-acetylcysteine, coumadin, bosentan, or etanercept). This article examines the body of evidence supporting the current therapies and reviews the newer agents being tested in patients with IPF.