The studies of global social and economic inequalities in social sciences that go beyond “methodological nationalism” are recent but have older roots. The first theories to reflect on the global and trans-regional interconnections and asymmetric regional developments within the capitalist system can be traced back to a Marxian tradition. These theories were critical to the conventional approach to social inequalities (hegemonic in the Western European and US academic centers in the 20th century) restricted to within nation-state boundaries. However, during the last three decades, several new approaches have emerged to capture the construction of social inequalities within the context of transnationalization, which extend beyond defined political units such as the nation-state. Transnationalization is creating a new challenge to social scientists to review critically their premises related to their reference units and to study social inequalities by focusing on social, economic, cultural and political interdependencies from the global perspective. This paper will focus specifically on four different approaches to global inequalities: (1) global and international comparative research; (2) the world-system perspective; (3) the transnational approach; and (4) the approach of entanglements. The aim is to draw a critical balance of these recent approaches, examine the central theoretical arguments and empirical findings, identify shortcomings and make suggestions for further research.