Improvement in tissue oxygenation by therapeutic angiogenesis was initially applied to ischemic hearts and occluded limbs. Future applications extend to other cardiac diseases, cardiac failure due to post–myocardial infarction remodeling, restenosis, diabetic neuropathy, and stroke. However, the risk:benefit ratio must be carefully weighed with regard to candidate conditions (taking into account risks such as promotion of tumor or atherosclerotic plaque growth) and patients (not only will many eligible patients have additional disease, raising difficult, often contradictory therapeutic options, but angiogenomic profiling is required to optimize and tailor angiogenic therapies to account for variations in individual response). The current challenge is to establish a unified framework to develop effective therapeutic strategies...