The stimulation of collateral artery growth (arteriogenesis) is a promising alternative approach to non-invasively treat arterial obstructive disease, such as coronary, peripheral or cerebral artery disease. Patients unable to undergo conventional revascularization strategies may benefit from adaptive arteriogenesis. Underlying mechanisms are experimentally validated and include an increase in shear stress after obstruction or occlusion of a major artery; monocyte adhesion, transmigration and perivascular accumulation, secretion of growth factors; and smooth muscle and endothelial cell proliferation and growth of pre-existent collateral arteries. Therapeutic stimulation of arteriogenesis with cytokines has been successfully performed in experimental models. Translation into clinical practice, however, has hitherto been problematic. Reasons for this include differences between the healthy laboratory animal and an often severely diseased patient, possible harmful effects of pro-arteriogenic therapies and unsuitable clinical endpoints for the detection of collateral artery growth. Recent investigations of human arteriogenesis demonstrate significant inter-individual differences and point towards the importance of anti-arteriogenic mechanisms in patients with impaired adaptive arteriogenesis and high cardiovascular risk factors.