Different forms of vessel growth in the adult organism contribute to the compensation for an occluded artery. We here summarize the major differences between arteriogenesis and angiogenesis and provide evidence in favour of a therapeutic stimulation of collateral growth. In addition, we outline current knowledge about regulatory mechanisms transducing the initial physical stimulus into a cellular response. As an example, the role of nitric oxide during arteriogenesis is discussed, and finally, we propose a mechanism of how an efficient decision is made that makes the larger collaterals larger and the smaller ones smaller. Copyright © 2012 John Wiley & Sons, Ltd.