The transforming growth factor-beta (TGF-beta) superfamily of receptors comprises two groups of transmembrane serine-threonine kinase receptors, so called type I, and type II receptors, that are activated following engagement by members of the TGF-beta superfamily of ligands. These events specify diverse downstream responses that are differentially regulated by controlling access and activation of the ligands, their receptors and downstream substrates in different cell types. The purpose of this review is to describe the biochemical properties of these receptors, focusing specifically on the mechanisms regulating receptor/ligand interactions and activation in mammalian cells.