Smad transcription factors play a central role in the transforming growth factor-β (TGFβ) signaling pathway, which is one of the most versatile cytokine signaling pathways in metazoan biology. Recent advancements have elucidated the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and the assembly of transcriptional complexes. The TGFβ family, consisting of 42 members in humans, seven in *Drosophila*, and four in *C. elegans*, exerts profound effects on cell division, differentiation, migration, adhesion, organization, and death. Smad proteins, which are ~500 amino acids long and consist of two conserved globular domains (MH1 and MH2) and a variable linker region, are key components of the TGFβ signaling pathway. They undergo a constant process of nucleocytoplasmic shuttling, with receptor-mediated phosphorylation events leading to their nuclear accumulation. The MH1 domain is a DNA-binding module that forms a β-hairpin structure for binding to DNA, while the MH2 domain is a versatile protein-interacting module that mediates interactions with various proteins and transcriptional cofactors. The formation of Smad transcriptional complexes involves the association with DNA-binding cofactors, which allows for high-affinity and selective targeting of specific genes. These complexes can recruit coactivators or corepressors, depending on the associated cofactor, and can also induce self-enabled gene response cascades and graded Smad response mechanisms. The role of Smad4 in these complexes is essential, and its absence can lead to reduced gene responses to TGFβ signaling. The specificity of Smad-mediated transcriptional regulation is determined by the combination of Smad partners and DNA-binding cofactors, providing four levels of specificity: target gene, pathway, cell type, and transcriptional effect.Smad transcription factors play a central role in the transforming growth factor-β (TGFβ) signaling pathway, which is one of the most versatile cytokine signaling pathways in metazoan biology. Recent advancements have elucidated the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and the assembly of transcriptional complexes. The TGFβ family, consisting of 42 members in humans, seven in *Drosophila*, and four in *C. elegans*, exerts profound effects on cell division, differentiation, migration, adhesion, organization, and death. Smad proteins, which are ~500 amino acids long and consist of two conserved globular domains (MH1 and MH2) and a variable linker region, are key components of the TGFβ signaling pathway. They undergo a constant process of nucleocytoplasmic shuttling, with receptor-mediated phosphorylation events leading to their nuclear accumulation. The MH1 domain is a DNA-binding module that forms a β-hairpin structure for binding to DNA, while the MH2 domain is a versatile protein-interacting module that mediates interactions with various proteins and transcriptional cofactors. The formation of Smad transcriptional complexes involves the association with DNA-binding cofactors, which allows for high-affinity and selective targeting of specific genes. These complexes can recruit coactivators or corepressors, depending on the associated cofactor, and can also induce self-enabled gene response cascades and graded Smad response mechanisms. The role of Smad4 in these complexes is essential, and its absence can lead to reduced gene responses to TGFβ signaling. The specificity of Smad-mediated transcriptional regulation is determined by the combination of Smad partners and DNA-binding cofactors, providing four levels of specificity: target gene, pathway, cell type, and transcriptional effect.