Introduction 3. Thrombospondin 3.1. The identification of thrombospondin-1 as a natural inhibitor of angiogenesis 3.2. Structure-function properties of thrombospondins 4. The role of CD36 in regulating angiogenesis 4.1. CD36: A multifunctional glycoprotein 4.2. The anti-angiogenic activity of TSP-1 is mediated by CD36 4.3. Downstream effects of TSP-1 interactions with CD36 5. The role of histidine-rich glycoprotein as a regulator of TSP-CD36 interactions 5.1. CD36-like homology motifs in HRGP 5.2. HRGP binding to TSP-1 5.3. HRGP inhibits the anti-angiogenic activity of TSP-1 6. The TSP-1/CD36 anti-angiogenic pathway in tumor angiogenesis 6.1. Transcriptional regulation of TSP-1 6.2. TSP-1/CD36 modulation in tumor models 6.3. Endothelial specificity of the TSP-1/CD36 anti-angiogenic system 7. Summary and perspective