Angiogenesis represents a major focus for novel therapeutic approaches to the prevention and treatment of multiple diseases, most notably ischemic cardiovascular disease and cancer. Therapeutic angiogenesis achieved either through the use of discreet angiogenic proteins or by gene therapy is fast emerging as a highly attractive treatment modality for ischemic heart disease. The purpose of this review is to address this important clinical issue through the identification of potential signaling mechanisms by which a short episode of sublethal ischemia known as ischemic preconditioning causes angiogenesis and subsequently improves myocardial salvage following coronary artery occlusion.