Angiotensin inhibitors are standard drugs in cardiovascular and renal diseases that have antihypertensive and antifibrotic properties. These drugs also exert their antifibrotic effects in cancer by reducing collagen and hyaluronan deposition in the tumor stroma, thus enhancing drug delivery. Angiotensin II signaling interferes with the secretion of the cytokine TGF-β—a known driver of malignancy. TGF-β stimulates matrix production in cancer-associated fibroblasts, and thus drives desmoplasia. The effect of TGF-β on cancer cells itself is stage-dependent and changes during malignant progression from inhibitory to stimulatory. The intracellular signaling for the TGF-β family can be divided into an SMAD-dependent canonical pathway and an SMAD-independent noncanonical pathway. These capabilities have made TGF-β an interesting target for numerous drug developments. TGF-β is also an inducer of epithelial–mesenchymal transition (EMT). EMT is a highly complex spatiotemporal-limited process controlled by a plethora of factors. EMT is a hallmark of metastatic cancer, and with its reversal, an important step in the metastatic cascade is characterized by a loss of epithelial characteristics and/or the gain of mesenchymal traits.