Hypoxia is an imbalance between oxygen supply and demand that occurs in cancer and in ischemic cardiovascular disease. Hypoxia-inducible factor 1 (HIF-1) was originally identified as the transcription factor that mediates hypoxia-induced erythropoietin expression. More recently, the delineation of molecular mechanisms of angiogenesis has revealed a critical role for HIF-1 in the regulation of angiogenic growth factors. In this review, we discuss the role of HIF-1 in developmental, adaptive and pathological angiogenesis. In addition, potential therapeutic interventions involving modulation of HIF-1 activity in ischemic cardiovascular disease and cancer will be discussed.