Comparative Area Studies (CAS) offers a template to bring the Global South back into the foreground of social science inquiry. CAS urges researchers to grapple directly with empirical variations derived from across the seemingly different global regions. CAS offers three comparative modes: intra-regional, cross-regional, and trans-regional. A number of scholars have used CAS’s comparative rubrics, even without knowing about the wider CAS agenda and program. CAS unsettles assumptions about discrete, fixed “regional” or civilizational blocks as well as about nomothetic theory-building aimed at universal or general laws. At the same time, CAS engages in the idea of medium-range theory-building, focusing empirical rigor and induction in order to create concepts and analyses that are portable yet contextualized. These macro-historical theories must be attentive to spatial and temporal variation in the social world. Claims of universalism are suspect. For the study of the Global South, in particular, CAS provides a path for aggregating and leveraging the wide range of observations and interpretations area specialists have to offer on regions as diverse as South Asia, the Middle East, Latin America, and sub-Saharan Africa. CAS thus changes the division of labor within social science to allow greater input for scholarship derived from and originating in the developing world.