The authors trace the history of the now-symbiotic relationship between universities and the scientific enterprise and indicate how remarkable and beneficial this relationship has been. But, at the same time, universities are beset with troubles, many of their own making, and some of their actions are now questioned by the public. The authors indicate the major problem areas and some reasons for them, and then focus on one of the most serious of the universities’ troubles, scientific fraud, which was once seen as a marginal problem but is now regarded as a central one by the public, who feel betrayed by the enterprise they are supporting. Just how much fraud actually occurs is hard to know; fraud is difficult to detect and fairly easy to perpetrate. The amount of damage that fraud, both detected and undetected, inflicts is also hard to estimate, but it can be considerable and of various types, one of the worst of which is the erosion of public confidence in the scientific enterprise. The authors urge universities and the scientists they support to be worthy of the public trust and to take seriously their responsibilities for setting, passing on, and enforcing the ethical standards of scientific research. They also propose reforms of some of the underlying conditions that make fraud more likely, so that the scientific enterprise will be strengthened from within, can continue to flourish, and will be worthy of public trust.