Background The societal discourse concerning gender(diversity) is changing rapidly and this trickles down to our consultation rooms. Most requests for gender-affirming medical care (GAMC) are well-considered and evidently necessary. In more complex presentations, however, challenges may arise. Aim To provide insight into clinical challenges in decision-making regarding GAMC. Method Discussing relevant literature by means of a clinical vignette. Results Dilemmas may arise in assessing competence to give consent to treatment. In differential diagnosis, it may be challenging to discern the interaction between gender incongruence and co-occurring mental conditions. Conclusion It is unethical to prima facie deny access to GAMC to those presenting with co-occurring mental health concerns and/or challenges in decision-making capacity. For this population, specialist care and comprehensive deliberation are indicated. To arrive at good care and decision-making, sufficient knowledge and sensitivity among, and cooperation with other mental health services is indispensable.