Interstitial lung diseases encompass a broad spectrum of disorders that vary greatly in their clinical presentation, natural history, pathology, pathogenesis, prognosis, and treatment. Their correct classification requires integration of clinical, radiological, and pathological findings. Although these disorders may be well defined, interpretation of lung biopsy findings is often difficult, with surprisingly significant interobserver variability. This article reviews the histopathology of the major interstitial lung diseases, including the idiopathic interstitial pneumonias and pulmonary fibrotic disorders associated with collagen vascular diseases and smoking. In addition, the differential diagnosis of each of these disorders is discussed.