The distortion of growth factor signalling is the most important prerequisite in tumour progression. Transforming growth factor-β (TGFβ) signalling regulates tumour progression by a tumour cell-autonomous mechanism or through tumour–stroma interaction, and has either a tumour-suppressing or tumour-promoting function depending on cellular context. Such inherent complexity of TGFβ signalling results in arduous, but promising, assignments for developing therapeutic strategies against malignant tumours. As numerous cellular context-dependent factors tightly maintain the balance of TGFβ signalling and contribute to the regulation of TGFβ-induced cell responses, in this Review we discuss how they maintain the balance of TGFβ signalling and how their collapse leads to tumour progression.