Coronary artery disease (CAD) and peripheral vascular disease (PVD) are significant medical problems worldwide, and arguably the biggest medical problems in the developed world. Although substantial progress has been made in prevention as well as in the treatment of these diseases, particularly of CAD, there are a large number of patients, who despite maximal medical treatment, have substantial symptomatology, and who are not candidates for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing, treatment option for these patients. Consequently, there are several different products in clinical trials, looking at various angiogenic growth factors. A number of small, mostly open-labeled phase I or phase I/II studies have been conducted with adeno- and plasmid-based vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) gene constructs in CAD and PVD. Although these studies have provided intriguing indications that new vessel formation is possible, and that these new vessels could be functional, these studies have been too small to allow conclusions to be drawn about potential efficacy. A number of proof-of-concept studies are presently underway or planned with four different constructs Ad(GV)VEGF121.10 (BioByPass; GenVec Inc), ph-VEGF (St Elizabeth's Medical Center of Boston Inc), Ad5-FGF4 (Collateral Therapeutics Inc/Schering Inc) and NV1FGF (Aventis Pharma AG/Aventis Gencell), and should, upon completion, provide a better indication as to the potential therapeutic role of these treatment modalities in the armamentarium against atherosclerotic disease. This exciting new field is reviewed, with special emphasis on clinical trials.