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From the early years of this century, many Western countries adopted the “Dutch Protocol” as a new medical pathway for treating children and adolescents with childhood-onset gender dysphoria. On this approach, gonadotrophin-releasing hormone agonists (GnRHa) were used to suppress puberty, followed by cross-sex hormones (testosterone or oestrogen). This perspective article traces—in each of the countries where we, the authors, live and work—how the Dutch Protocol came to be incorporated into clinical practice or formally adopted into national guidelines. Over time, guidelines across different countries were progressively shaped by a rights-based approach that removed previous safeguards and increased availability of gender-reassignment medical interventions for children and adolescents. From 2010 onward, two developments raised new concerns, generating alternate perspectives and wide-ranging differences in clinical approach. Numerous countries reported an unexpected increase in adolescent-onset presentations, especially among girls. During the same period, an increasing number of individuals who had undergone gender-reassignment medical interventions as minors reported harm and regret. Worldwide, questions were raised about the safety of clinical guidelines for children and adolescents presenting with gender dysphoria. Government bodies in Finland, Sweden, the United Kingdom, and the U.S. state of Florida commissioned systematic reviews pertaining to hormone treatments and issued formal reports. In a parallel process, “conversion therapy” laws, passed in many countries, closed access to exploratory psychotherapy that enables exploration of gender-identity issues from a neutral therapeutic stance. Taken together, these three developments introduced evidence-based and legal considerations into the debate, resulting in tensions that remain unresolved.