Idiopathic pulmonary fibrosis (IPF) is a devastating, lethal and currently untreatable lung disorder of unknown etiology. It is characterized by epithelial injury and activation, fibroblastic foci formation, and exaggerated accumulation of extracellular matrix (ECM) with the destruction of the lung parenchyma. Despite important progress in our understanding of the general mechanisms involved in lung fibrogenesis, the pathogenesis of the IPF remains unclear. Although the irreversible and progressive fibrosis in the lung suggests a decrease in lung degradative machinery, an increasing body of evidence, primarily obtained by global gene expression studies, demonstrates a significant upregulation of degrading enzymes in IPF. In this context, this review will focus on some families of the degradome, a term proposed for the complete set of proteases that are expressed at a specific time by a cell, tissue or an organism. In particular, we will approach recent progress in our understanding of the behavior of two families of metalloproteases M10 and M12 which are significantly changed in the IPF lungs. In general, evidence highlights the increasing diversity in both substrates and functions of these enzymes and the complexity of the processes in which they are involved, and indicate a critical role in the abnormal remodeling of IPF.