Despite the continuous and renewed interest in IPF, the precise biological mechanisms underlying the development of fibrosis and leading to the irreversible destruction of the lung are still unknown. Inflammation seems to play a minor role at the initiation of the disease. Identification of excessive apoptosis of alveolar epithelial cells led to the hypothesis that the disorder results from repeated alveolar epithelial cell injury and activation. In turn, alveolar epithelial cells induce the recruitment, proliferation, and activation of mesenchymal cells with the formation of fibroblastic foci and the abnormal accumulation of extracellular matrix. Fibroblastic foci are connected in a tridimensional reticulum. Circulating mesenchymal precursors called fibrocytes, and transdifferenciation of epithelial cells, endothelial cells and/or mesothelial cells, may all contribute to the accumulation of fibroblasts in the lung.