Protein and gene therapy offer a tremendous opportunity to improve the care of critically ill patients with ischemic heart and peripheral artery occlusion disease. With the availability of purified growth factors such as vascular endothelial and fibroblast growth factors (FGF), several experimental and clinical studies provided data, that the growth of capillaries (angiogenesis) and of collateral arteries (arteriogenesis) is not limited to its natural time course. When applied in experimental models and in conjunction with coronary artery bypass operations, FGF in particular, led to a significant increase in endogenous rerouting of blood flow by collateral vessels inside the tissue itself. Thus, the proliferation of preexisting bypassing arterioles could be enhanced therapeutically (biological bypass). The purpose of this review is to discuss the physiological importance of different kinds of cytokines which are able to induce angio- and arteriogenesis in ischemic limbs or the heart. It is outlined that a combination of a sufficient amount of large arterioles and a capillary network are needed to compensate perfusion deficits. Each patient, who has an ischemic area and cannot be conventionally revascularized, is a potential candidate for the biological bypass.