Gender dysphoria can be a devastating condition but the symptoms are not always straightforward or visible. In this clinical lesson three cases are presented in which GPs suspect gender dysphoria in their patient but are not sure of the best approach. These cases illustrate how gender identity can sometimes vary or develop over time, and how in complex cases psychiatric co-morbidity can interfere with gender identity development and with the treatment of gender dysphoria. The article gives examples of how to discuss the topic with the patient. Furthermore, it describes the referrals and the general support a GP can give during a gender reassignment process.