Iodothyronines stimulate neovascularization in tumor beds, brain, ischemic myocardium and striated muscle. The molecular basis of the action can be studied in models such as the chick chorioallantoic membrane (CAM) and human microvascular endothelial cell (HDMEC) microtubule formation. Nongenomic and genomic actions of the hormone may contribute to angiogenesis. The initial description of the cell surface receptor for thyroid hormone (T4 and 3,5,3′-triiodo-L-thyronine T3) on integrin αvβ3 nongenomically linked thyroid hormone to angiogenesis via mitogen-activated protein kinase (MAPK; ERK1/2) and involved downstream transcription of basic fibroblast growth factor (bFGF, FGF2) and vascular endothelial growth factor (VEGF) genes. Further, crosstalk between the hormone receptor on the integrin and VEGF and bFGF receptors clustered with the integrin has also been demonstrated. Other pro-angiogenic hormone analogues are diiodothyropropionic acid (DITPA) and GC-1. Tetraiodothyroacetic acid (tetrac) is an inhibitor of the actions of T4 and T3 at the integrin and blocks thyroid hormone-induced angiogenesis. In the absence of T4 and T3, however, tetrac will also inhibit the actions of VEGF, platelet-derived growth factor (PDGF) and bFGF in CAM and HDMEC microtubule assays. Iodothyronines may also stimulate angiogenesis about areas of infarction in the myocardium in the intact experimental animal by a mechanism that may involve TRβ. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor important to ischemia-induced coronary artery collateralization; acting in cytoplasm, T3 induces expression of the HIF1α gene. Thus, thyroid hormone is pro-angiogenic by mechanisms that may begin at the plasma membrane, in cytoplasm or within the nucleus. Pro-angiogenic actions of the hormone initiated at the integrin may involve crosstalk at the cell surface with vascular growth factor receptors or, downstream, culminate in vascular growth factor gene expression. Acting at the integrin, tetrac is anti-angiogenic by inhibiting actions of T4 and T3 and by blocking effects of VEGF, bFGF and PDGF.