Colorectal cancer remains the most common cancer and the second leading cause of cancer mortality in Europe. There are a number of pathways that have been implicated in colorectal carcinogenesis, including TGF-beta (TGF-β)/Smad signalling pathway. The TGF-β pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Here we review the role of TGF-β signalling cascade in colorectal carcinogenesis and provide some new molecular insights that may aid efforts towards targeted antitumor therapies.