This essay addresses the paradox that, while transnationalization can only adequately be tested by cross-national comparative designs, it also undermines a premise of these designs—namely, to think of systems as self-contained things that can be independently compared. I will resolve this apparent dilemma by making several suggestions as to how traditional approaches need to be updated. First, I will outline the logic of comparative analysis. Next, I will explain its scientific relevance and justify its emerging status as an autonomous subfield in the communication discipline. Finally, I will explicate how comparative designs must be amended to account for the challenges of transnationalization.