Transforming growth factor-β (TGF-β) is extensively involved in the development of fibrosis in different organs. Overproduction or potentiation of its profibrotic effects leads to an aberrant wound healing response during the initiation of fibrotic processes. Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating disease, in which TGF-β\x{2013}induced disturbances of the homeostatic microenvironment are critical to promote cell activation, migration, invasion, or hyperplastic changes. In addition, excess extracellular matrix production contributes in a major way to disease pathogenesis. For this reason, this review will focus on discussing novel data and highlight growing interest in deepening the understanding of the profibrotic role of TGF-β and its direct or indirect targeting for disease modulation.