Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive disease, marked by excessive scarring, which leads to increased tissue stiffness, loss in lung function and ultimately death. IPF is characterised by progressive fibroblast and myofibroblast proliferation, and extensive deposition of extracellular matrix (ECM). Myofibroblasts play a key role in ECM deposition. Transforming growth factor (TGF)-β1 is a major growth factor involved in myofibroblast differentiation, and the creation of a profibrotic microenvironment. There is a strong link between increased ECM stiffness and profibrotic changes in cell phenotype and differentiation. The activation of TGF-β1 in response to mechanical stress from a stiff ECM explains some of the influence of the tissue microenvironment on cell phenotype and function. Understanding the close relationship between cells and their surrounding microenvironment will ultimately facilitate better management strategies for IPF.