In 2001, in response to identified barriers to the efficient development of cancer therapeutics, one of us called for a comprehensive reappraisal of the national program, including the policies of the Food and Drug Administration (FDA; ref. 1). Concern was expressed that the systems for cancer therapy development had remained basically unchanged for a period of three decades. Despite the growing scientific opportunities and significant investment being made by all sectors, the output of new cancer therapies reaching the public in the form of FDA-approved products was insufficient to meet the needs of patients. The message was largely received with deafening silence. This was not unexpected because one of the issues raised in the review was the basic state of complacency within the scientific community. In a follow-up article, we evaluated the productivity of the National Cancer Program using the metrics of numbers and indications of new cancer therapeutics reaching the public (2). We once again concluded that there was significant lost opportunity; in order for the multibilliondollar public-private investment in the National Cancer Program to fulfill its mandate to reduce morbidity and mortality, a bold commitment to revisit the entire menu of policies that affect the timely delivery of scientific advances would be required. There are now indications that the message has registered with the FDA, and that changes, such as the Critical Path initiative, are being implemented to provide a more responsive regulatory environment (3, 4); other sectors, however, have remained largely silent. In this brief review, we provide a restatement of the problem and provide several recommendations for improving the model. By any objective assessment, there can be little doubt that cancer is one of the most important issues facing our society. In 2005, the incidence in the United States was> 1.3 million; f50% of American men and one third of women are afflicted sometime in their lives. There were an estimated 600,000 deaths due to cancer, thus accounting for approximately one fourth of all deaths in the United States and forming the leading cause of death for all individuals under the age of 75 years (5). The costs of cancer measured in pure economic terms (ie, direct medical expenses and lost productivity) is increasing at an exponential rate and is currently estimated to be in excess US $190 billion (5).