The American system of higher education is under attack by political, economic, and educational forces that threaten to undermine its business model, governmental support, and operating mission. The potential changes are considerably more dramatic and disruptive than anything previously experienced. Traditional colleges and universities urgently need a coherent, thought-out response. Their central role in fostering the creation, preservation, and distribution of knowledge in the world may be at risk and, as a consequence, so too may be the spectacular progress across fields we have come to expect as a result.