For more than two decades experts have predicted that the US higher education system was headed toward systemic change. Many signs now point to a conclusion that we have reached that inflection point. The severe economic downturn of the past six years, combined with major demographic shifts and dislocating technological change, have exposed serious structural weaknesses in the US system that pose significant threats to all but elite tier institutions. This paper examines the current state of US higher education in light of these forces. It discusses the implications of innovative technologies and practices, as well as how institutions might use them to adapt and thrive in a higher education world turned upside-down.