Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have been studied for over 25 years as models for growth factor and receptor tyrosine kinase function. PDGF signaling plays critical roles in animal development, including gastrulation, cranial and cardiac neural crest development, gonads, lung, intestine, skin, CNS, and skeleton. PDGFR-α signaling is involved in blood vessel formation and early hematopoiesis, while PDGFR-β signaling is implicated in various diseases, including gliomas, sarcomas, and leukemias. PDGF signaling is also involved in epithelial cancers, where it promotes stromal recruitment and epithelial–mesenchymal transition, affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological responses in vascular disorders and fibrotic diseases. PDGFs were first identified as serum growth factors for fibroblasts, smooth muscle cells, and glia cells. Human PDGF consists of two polypeptide chains, A and B, forming a disulfide-linked dimer. PDGF-A and PDGF-B are key ligands, with PDGF-A being expressed in epithelial cells, muscle, and neuronal progenitors, while PDGF-B is mainly expressed in vascular endothelial cells, megakaryocytes, and neurons. PDGFR-α is expressed in mesenchymal cells, while PDGFR-β is expressed in vascular smooth muscle cells and pericytes. PDGF signaling is regulated by various mechanisms, including receptor dimerization, intracellular processing, and extracellular retention. PDGFs are involved in developmental processes such as gastrulation, cranial and cardiac neural crest development, and organogenesis. PDGF signaling is also crucial for cell migration, with PDGF-A and PDGFR-α playing a role in directing mesodermal cell migration during gastrulation. PDGF signaling is involved in the formation of large specialized epithelial surfaces, such as the lung and intestine, where alveolar septum formation is critical. PDGF signaling is also involved in pathological conditions, including fibrosis and vascular disorders. PDGF signaling is regulated by various mechanisms, including receptor internalization, feedback control, and the action of kinases and phosphatases. PDGF signaling is a target for pharmacological inhibition, with drugs such as imatinib being used to treat diseases involving PDGF signaling. PDGF signaling is also involved in the development of various tissues, including the neural crest, and its disruption can lead to severe developmental defects. Overall, PDGF signaling plays a critical role in both physiological and pathological processes, highlighting its importance in development and disease.Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have been studied for over 25 years as models for growth factor and receptor tyrosine kinase function. PDGF signaling plays critical roles in animal development, including gastrulation, cranial and cardiac neural crest development, gonads, lung, intestine, skin, CNS, and skeleton. PDGFR-α signaling is involved in blood vessel formation and early hematopoiesis, while PDGFR-β signaling is implicated in various diseases, including gliomas, sarcomas, and leukemias. PDGF signaling is also involved in epithelial cancers, where it promotes stromal recruitment and epithelial–mesenchymal transition, affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological responses in vascular disorders and fibrotic diseases. PDGFs were first identified as serum growth factors for fibroblasts, smooth muscle cells, and glia cells. Human PDGF consists of two polypeptide chains, A and B, forming a disulfide-linked dimer. PDGF-A and PDGF-B are key ligands, with PDGF-A being expressed in epithelial cells, muscle, and neuronal progenitors, while PDGF-B is mainly expressed in vascular endothelial cells, megakaryocytes, and neurons. PDGFR-α is expressed in mesenchymal cells, while PDGFR-β is expressed in vascular smooth muscle cells and pericytes. PDGF signaling is regulated by various mechanisms, including receptor dimerization, intracellular processing, and extracellular retention. PDGFs are involved in developmental processes such as gastrulation, cranial and cardiac neural crest development, and organogenesis. PDGF signaling is also crucial for cell migration, with PDGF-A and PDGFR-α playing a role in directing mesodermal cell migration during gastrulation. PDGF signaling is involved in the formation of large specialized epithelial surfaces, such as the lung and intestine, where alveolar septum formation is critical. PDGF signaling is also involved in pathological conditions, including fibrosis and vascular disorders. PDGF signaling is regulated by various mechanisms, including receptor internalization, feedback control, and the action of kinases and phosphatases. PDGF signaling is a target for pharmacological inhibition, with drugs such as imatinib being used to treat diseases involving PDGF signaling. PDGF signaling is also involved in the development of various tissues, including the neural crest, and its disruption can lead to severe developmental defects. Overall, PDGF signaling plays a critical role in both physiological and pathological processes, highlighting its importance in development and disease.