Signals from the transforming growth factor-β (TGF-β) superfamily mediate a broad spectrum of cellular processes and are deregulated in many diseases, including cancer. TGF-β signaling has dual roles in tumorigenesis. In the early phase of tumorigenesis, TGF-β has tumor suppressive functions, primarily through cell cycle arrest and apoptosis. However, in the late stage of cancer, TGF-β acts as a driver of tumor progression and metastasis by increasing tumor cell invasiveness and migration and promoting chemo-resistance. Here, we briefly review the mechanisms and functions of TGF-β signaling during tumor progression and discuss the therapeutic potentials of targeting the TGF-β pathway in cancer.