The transforming growth factor (TGF)-betas are potent growth inhibitors of normal epithelial cells. In established tumor cell systems, however, the preponderant experimental evidence suggests that TGF-betas can foster tumor-host interactions that indirectly support the viability and/or progression of cancer cells. The timing of this 'TGF-beta switch' during the progressive transformation of epithelial cells is not clear. More recent evidence also suggests that autocrine TGF-beta signaling is operative in some tumor cells, and can also contribute to tumor invasiveness and metastases independent of an effect on nontumor cells. The dissociation of antiproliferative and matrix associated effects of autocrine TGF-beta signaling at a transcriptional level provides for a mechanism(s) by which cancer cells can selectively use this signaling pathway for tumor progression. Data in support of the cellular and molecular mechanisms by which TGF-beta signaling can accelerate the natural history of tumors will be reviewed in this section.