Despite considerable progress in the management of ischaemic cardiovascular disease during the past three decades, there remains a significant population of patients who are not served well by current treatment approaches. Stimulating revascularization in ischaemic regions is an attractive novel therapeutic strategy, and several angiogenic agents anticipated to have the potential to achieve this goal have been clinically evaluated in recent years. However, as yet none have shown sufficient efficacy to be approved. Here, we consider the key findings from the completed clinical trials of therapeutic angiogenesis in cardiovascular disease, and discuss possible changes to the way in which such agents are developed that could improve the chances of success.