Fibroproliferative lung disease is prevalent and associated with high mortality. The pathogenesis of fibrotic lung disease involves inflammation, mesenchymal cell proliferation, and deposition of interstitial matrix components, such as collagen and fibronectin. Corticosteroids and other immunosuppressive medications have been routinely employed, but have demonstrated only marginal efficacy. Even though this information has been known for some time, the optimal medical regimen for treating pulmonary fibrosis remains largely undefined. This article addresses the rationale for, and efficacy of, antifibrotic regimens used to treat humans with fibrotic lung diseases.