With rapid socio-economic changes, twenty-first century higher education is facing major challenges to its governance systems, curriculum, mission focus, external relations, research, and financing. A theoretical framework to analyze these post-massification challenges is suggested, with a focus on the Asia-Pacific region as well as global issues. Five main topic areas provide the basis for the theoretical framework: massification, privatization, accountability and governance, internationalization, and ranking and world-class universities. Some discussion of the possible effects of the financial crisis that commenced in 2008 is provided.