Autogenous vein is the conduit of choice in the surgical creation of bypasses of small-to-medium-caliber vessels in patients with peripheral occlusive arterial disease and will remain so for the near future. The success rate of bypasses using conduits of diameters greater than 6 mm has been excellent, whereas the majority of bypasses using smaller conduits fail within 5 years. In addition, due to a steep increase in rates of diabetes and decreasing cardiovascular mortality rates, increasing challenges are presented by this population. These facts have motivated much of the research in the cardiovascular arena over the past four decades, with improved techniques and new materials. Strategies to improve outcomes include the use of alternative materials including autologous, nonautologous and prosthetic grafts, utilizing different methods for their harvesting and preservation; tissue engineering, using either polymer- or biological-based scaffolds for cell seeding; endovascular methodologies; and gene therapy. This report presents an overview of the several options currently available in the management of patients with peripheral arterial occlusive disease, as well as the ongoing research directed towards the creation of an artificial engineered vessel, discussing experimental work in which endothelial cells have been seeded on different scaffolds and finally the potential application of gene therapy in the field of vascular reconstruction.