The following report is based on a working group meeting about advanced coronary artery disease for patients with refractory ischemia who cannot receive revascularization. The aims were to review currently available treatment strategies, define unmet clinical needs, explore clinical trial design issues, and identify promising novel therapeutic targets and approaches for patients with chronic ischemia. The Working Group brought together medical experts in the management of refractory angina with representatives from regulatory agencies, Centers for Medicare and Medicaid Services, and industry. The meeting began with presentations reviewing the limitations of the current medical therapies and revascularization strategies and focused on lessons learned from past therapeutic attempts to optimize outcomes and on what are considered to be the most promising new approaches. Perspectives from clinical experts and from regulatory agencies were juxtaposed against needs and concerns of industry regarding development of new therapeutic strategies. This report presents the considerations and conclusions of the meeting on December 4-5, 2006. This document has been developed as a 2-part article, with contemporary and emerging therapies for advanced coronary artery disease reviewed first. Trial design, end points, and regulatory issues will be discussed in the second part of the article.