The discovery of the transforming growth factor b (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF- β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF- β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF- β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as “sink” and control storage and release of both the TGF- β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF- β family signals. This article reviews our knowledge of extracellular modulation of TGF- β growth factors by diverse proteins and their molecular mechanisms to regulate TGF- β family signaling.