Low oxygen environment or hypoxia is conducive towards vascular growth and endothelial proliferation. Therefore it is an essential element in both disease and development. Hypoxia stabilizes the hypoxia-inducible transcription factors-1α and -2α and also increases adenosine levels thereby activating the adenosine receptor signaling pathways. While these pathways have been described independently to a greater extent, increasing evidence suggests that there is significant crosstalk. Here we will summarize the contributions and interdependence of hypoxia-inducible transcription factors and the adenosine receptor pathways in vascular growth. © Springer Science+Business Media B.V. 2010.