The medical classifications of transgender identities have evolved over time from "gender identity disorder" in DSM-IV to "gender dysphoria" in DSM-5 and more recently “gender incongruence” in ICD-11, in an attempt to reduce stigmatization by separating gender identity from associated discomfort/dysphoria. The transgender term covers a wide spectrum of gender variants. The difficulties in establishing a rigorous differential diagnosis compared to other mental disorders that manifest similarly are discussed, such as delusional, obsessive-compulsive or certain personality disorders. The distinction from transvestic fetishism with increased tolerance to crossdressing is also problematic. Specific psychological and psychiatric assessment tools are essential. Current controversies regarding the clinical management of gender incongruence in minors are presented. Some experts recommend postponing irreversible medical treatments, others support early access to them. The consensus is that decisions should be individualized, with caution in the case of minors. The need for formal differential diagnosis guidelines and establishing the most appropriate therapeutic strategies for transgender subgroups is emphasized, in order to provide optimal and individualized medical care. Optimizing the clinical assessment process and monitoring during transition are vital. Interdisciplinary collaboration and family support are essential. Further research is needed to develop these diagnosis guidelines and therapeutic strategies tailored to the varied experiences of transgender individuals.