The role of serotonin reuptake inhibitors (SSRIs) in treating psychiatric disorders has been a subject of heated debate since their introduction. Initially celebrated for their potential to address various mental health conditions during the late 1980s and 1990s, SSRIs have since faced significant scrutiny. Critics argue that their benefits may not be as substantial as initially believed. Over the past two decades, concerns have intensified with the emergence of boxed warnings about the risks associated with SSRIs, particularly regarding their link to increased suicidal thoughts in youth. This controversy is further complicated by questions about the integrity of early industry-sponsored trials and the reliability of subsequent National Institute of Mental Health (NIMH) trials. These issues have raised ongoing critical concerns about the effectiveness and safety of SSRIs, especially for treating a range of disorders in children and adolescents. This review seeks to critically appraise by presenting empirical evidence that addresses these controversies. It explores the validity of the monoamine theory, examines the fidelity of early and recent trials, and considers the broader implications for clinical practice. By answering specific, targeted questions, this article aims to clarify the ongoing debate and enhance the understanding of SSRIs’ role in mental health treatment. The goal is to support clinicians in making more informed decisions when prescribing these medications and to ensure consideration of the balance between potential benefits and risks for young patients with mental health disorders.