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International regimes for human protection have expanded over the past three decades. Yet, their effectiveness has been impaired by weak and selective implementation patterns. This paper explores the roles of regional institutions in the Global South, especially regional courts and tribunals, in promoting implementation of international protection commitments. As legal scholars have argued, regional courts empower transnational private actors and other compliance constituencies at the national level. But in addition, regional and sub-regional courts interpret and apply both multilateral and extra-regional laws in their adjudications and generate jurisprudence that subsequently influences outcomes in domestic courts within and beyond their region. To illustrate these mechanisms of cross-regime interactions, I use evidence from regional courts contributing to implementation of international norms for the protection of indigenous peoples’ rights, refugees and migrant workers, and human trafficking victims. I also trace how the inter-regional interactions between courts and tribunals in the Americas, Africa, and Europe have contributed to mitigating the selective implementations of these international norms.