Many human diseases are characterized by vasculature disorders. Out of the many players in the angiogenic network, the vascular endothelial growth genes are by far the best characterized. The vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of coronary artery disease (CAD) and in its complication, the acute myocardial infarction (AMI). Several common polymorphisms in the promoter region of the VEGF gene have been reported, but only few single nucleotide polymorphisms (SNPs) have been demonstrated to be associated with variations in VEGF serum concentrations and with a susceptibility to CAD and its complications-acute coronary syndromes. Moreover, the -634 C/G VEGF SNP (rs2010963) has been demonstrated to be associated with AMI and the development of heart failure after AMI. Gene-based therapy for patients with refractory CAD has been the subject of extensive investigation. Preclinical studies have shown promise for the delivery of VEGF gene for treating CAD, whereas the results of randomized placebo-controlled trials have not demonstrated unequivocal evidence of efficacy. To conclude, at present the role of VEGF and VEGF SNPs in pathogenesis of AMI and the development of heart failure after AMI is still uncertain and remains to be determined. Obviously, larger studies as well as functional studies are needed to confirm the role of VEGF SNPs in AMI and its complications after AMI.