This introductory article to the special issue takes stock of the scholarly impact of the last fifteen years of Global South studies scholarship in the field of literary and cultural studies, and comparative literature in particular. It contends that the Global South offers a dynamic framework for comparison of economic, political, and cultural inequalities beyond state-centric forms of analysis, and for this reason, is uniquely germane to the interests of comparative literature. The Global South has become a significant category for the field not in spite of its conceptual indeterminacy, but precisely because the resulting lack of fixity provides an adaptive and multiscalar comparative framework. That is, it offers an opportunity to shift the scale through which we compare, in which North–South or South–South analysis may occur across national lines or from block to block. True to the relational and directional spirit of the concept, the editors understand Global South studies as a series of directions or movements, a confluence of critical currents emerging from a variety of already existing fields. Ultimately, this introduction traces those critical coordinates and points to recent and promising directions in this scholarship as it intersects with comparative literature today.