Transforming growth factor-beta (TGF-beta) is an ubiquitous cytokine that affects various biological processes, such as regulation of cell proliferation, immune responses, growth, differentiation, angiogenesis, and apoptosis of various cell types. The TGF-beta ligand initiates signaling by binding to and joining type I and II receptors of serine/threonine kinases. This review discusses the TGF-beta ligands and receptors, its positive and negative regulators in signaling, as well as its important roles with respect to tumor suppression and progression.