Display omitted •Summary of the basic studies, patents, and clinical trials inhibiting TGF-β signalling, a critical pathway in tumorigenesis and fibrosis.•Small molecular inhibitors and neutralizing antibodies against TGF-β signaling are potential strategies for cancer therapy.•Natural products and repurposed drugs should continue to be major resources for screening TGF-β inhibitors.•The future prospect of new sources and mechanisms of TGF-β inhibitors are discussed in this review. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that is involved in proliferation, metastasis, and many other important processes in malignancy. Inhibitors targeting TGF-β have been considered by pharmaceutical companies for cancer therapy, and some of them are in clinical trial now. Unfortunately, several of these programs have recently been relinquished, and most companies that remain in the contest are progressing slowly and cautiously. This review summarizes the TGF-β signal transduction pathway, its roles in oncogenesis and fibrotic diseases, and advancements in antibodies and small-molecule inhibitors of TGF-β.