Besides signaling serine/threonine kinases, such as TGF-β receptors I and II, the TGF-β pathway involves several auxiliary receptors or coreceptors. Recent studies show that these coreceptors, particulary endoglin and β-glycan, have greater significance than previously thought. They regulate the availability of ligands to the key receptors, as well as their interaction and response, which could be variable and context-dependent. Understanding their true mechanism of action is important for delineating the complexity of the entire TGF-β signaling pathway. This is especially important in the context of cancerogenesis, because of therapeutic possibilities to manipulate the TGF-β system.