National media systems are the central units of analysis in comparative mass communication research. In times of growing globalization, however, it is increasingly difficult to treat national media systems as isolated cases — a dilemma that undermines the traditional logic of comparative research. A careful examination of the core conceptual challenges leads this article to conclude that global processes of diffusion do by no means spell the end of the comparative research of media systems. Global processes of diffusion do however demand for comparative designs that account for the fact that national media systems are becoming increasingly interconnected. This article makes three practical suggestions to tackle these challenges: The first suggestion is to include additional levels of analysis below and above the nation state level; the second suggestion is to incorporate theories from the field of International Communications; and the third is to remain cautious about the extent to which globalization penetrates national media systems. There is still reason to presume that media systems can be compared along the lines of national boundaries. We are required to modify and extent our tools though.