The growth of new blood vessels from the preexisting vascular tree, also known as angiogenesis, occurs in situations such as wound and fracture healing, arthritis, cardiovascular and cerebral ischemia, and nearly every type of cancer known. Vascular endothelial growth factor (VEGF) has been shown to play a crucial role in these events. Hypoxia-dependent VEGF induction is mediated by hypoxia-inducible factor-1 (HIF-1). HIF-1 is a heterodimeric transcription factor tightly regulated by oxygen concentration. In this short review, we summarize recent data concerning the control of HIF-1 activity and notably the regulation of HIF-1α subunit by phosphorylation and the ubiquitin proteasomal degradation system. A complete knowledge of this mechanism could, by the design of new antiangiogenic strategies, have a strong impact in clinical oncology.