Over the past two decades, depression has become a prominent global public health concern, especially in low- and middle-income countries (LMICs). The World Health Organization (WHO) and the Movement for Global Mental Health have developed international guidelines to improve mental health services globally, prioritizing LMICs. These efforts hold promise for advancing care and treatment for depression and other mental, neurological, and substance abuse disorders in LMICs. The intervention guides, such as the WHO's mhGAP-Intervention Guides, are evidence-based tools and guidelines to help detect, diagnose, and manage the most common mental disorders. Using the Global South as an empirical site, this article draws on Foucauldian critical discourse and document analysis methods to explore how these international intervention guides operate as part of knowledge-power processes that inscribe and materialize in the world in some forms rather than others. It is proposed that these international guidelines shape the global discourse about depression through their (re)production of biopolitical assumptions and impacts, governmentality, and “conditions of possibility.” The article uses empirical data to show nuance, complexity, and multi-dimensionality where binary thinking sometimes dominates, and to make links across arguments for and against global mental health. The article concludes by identifying several resistive discourses and suggesting reconceptualizing the treatment gap for common mental disorders.