This article summarizes the major integrin-ligand interactions, focusing on the structural and functional aspects of integrin binding. Integrins are heterodimeric cell adhesion receptors composed of α and β subunits. There are 18 α subunits and 8 β subunits in mammals, forming 24 different αβ combinations. Integrins bind to a variety of ligands, and their interactions are often promiscuous. The article discusses four main classes of integrin-ligand interactions: RGD-binding integrins, LDV-binding integrins, A-domain β1 integrins, and non-αA-domain-containing laminin-binding integrins. RGD-binding integrins, such as αVβ3 and αIIbβ3, recognize ligands with an RGD tripeptide. These integrins are among the most promiscuous, binding to many extracellular matrix and soluble vascular ligands. LDV-binding integrins, including α4β1, α4β7, and α9β1, recognize an acidic motif called LDV. The β2 family binds via an inserted A-domain in the α subunit. A-domain β1 integrins, such as α2β1, bind collagen through a collagenous GFOGER motif. Non-αA-domain-containing laminin-binding integrins, such as α3β1, α6β1, and α7β1, bind laminin in different regions. The article also lists additional integrin-ligand interactions, including ADAM family members, COMP, connective tissue growth factor, Cyr61, E-cadherin, ESM-1, fibrillin, fibrinogen, fibronectin, ICAM-4, LAP-TGFβ, MMP-2, nephronectin, L1, plasminogen, POEM, tenascin, thrombospondin, VEGF-C, VEGF-D, and vitronectin. Evolutionary analysis suggests that integrins evolved from two primordial types: one laminin-specific and one RGD-specific. The urochordate Ciona intestinalis has a unique set of integrins, with some subunits related to vertebrate αA-domains. The article concludes with acknowledgments of funding and contributions.This article summarizes the major integrin-ligand interactions, focusing on the structural and functional aspects of integrin binding. Integrins are heterodimeric cell adhesion receptors composed of α and β subunits. There are 18 α subunits and 8 β subunits in mammals, forming 24 different αβ combinations. Integrins bind to a variety of ligands, and their interactions are often promiscuous. The article discusses four main classes of integrin-ligand interactions: RGD-binding integrins, LDV-binding integrins, A-domain β1 integrins, and non-αA-domain-containing laminin-binding integrins. RGD-binding integrins, such as αVβ3 and αIIbβ3, recognize ligands with an RGD tripeptide. These integrins are among the most promiscuous, binding to many extracellular matrix and soluble vascular ligands. LDV-binding integrins, including α4β1, α4β7, and α9β1, recognize an acidic motif called LDV. The β2 family binds via an inserted A-domain in the α subunit. A-domain β1 integrins, such as α2β1, bind collagen through a collagenous GFOGER motif. Non-αA-domain-containing laminin-binding integrins, such as α3β1, α6β1, and α7β1, bind laminin in different regions. The article also lists additional integrin-ligand interactions, including ADAM family members, COMP, connective tissue growth factor, Cyr61, E-cadherin, ESM-1, fibrillin, fibrinogen, fibronectin, ICAM-4, LAP-TGFβ, MMP-2, nephronectin, L1, plasminogen, POEM, tenascin, thrombospondin, VEGF-C, VEGF-D, and vitronectin. Evolutionary analysis suggests that integrins evolved from two primordial types: one laminin-specific and one RGD-specific. The urochordate Ciona intestinalis has a unique set of integrins, with some subunits related to vertebrate αA-domains. The article concludes with acknowledgments of funding and contributions.