The transforming growth factor β (TGF-β) family controls many fundamental aspects of cellular behavior. With advances in the molecular details of the TGF-β signaling cascade and its cross talk with other signaling pathways, we now have a more coherent understanding of the cytostatic program induced by TGF-β. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated by TGF-β and determine a cell’s proliferation and survival, apoptosis, dormancy, autophagy, and senescence. The difficulty in defining TGF-β’s roles partly stems from the context-dependent nature of TGF-β signaling. Here, we review our current understanding and recent progress on the biological effects of TGF-β at the cellular level, with the hope of providing a framework for understanding how cells respond to TGF-β signals in specific contexts, and why disruption of such mechanisms may result in different human diseases including cancer.