The vascular endothelial growth factor A (VEGF-A) is essential during embryonic development as inactivation of only one allele of its gene results in embryonic lethality. Up-regulation of VEGF under physiological situations allows for adaptation to hypoxic stress, to transient inflammatory processes, and to wounding. Its expression also increases all along the process of neovascularization of solid and hematological tumors. The object of this article is to focus on the transcriptional regulation of its gene. The major cis-acting sequences and trans-activating factors will be described as well as the physiological and pathological situations leading to the intervention of such sequences and factors. We will also focus on two transcription factors essential to VEGF gene transcription: the hypoxia-inducible factor-1, which is responsible for its increased by hypoxia, as well as Sp1, which is implicated in the response to various extracellular stimuli.