This article provides the first systematic examination of the ways ‘talk about sex’ is occasioned and managed by doctors and patients in real-life interactions in a National Health Service Gender Identity Clinic. Drawing on a corpus of 194 recordings of psychiatric assessment sessions, the article examines how parties initiate and develop talk about sex, and which strategies appear to work best for doctor–patient alignment. The analyses revealed that the most aligning methods were for clinicians to make transitions from asking questions about relationships in general to talk about sex, or to build opportunistically on patients’ relationship talk. However, talk about sex that lacked specificity or which made inaccurate presumptions about patients’ sex lives, generated misalignment between clinician and patient. I suggest that such misalignment is not intrinsically bad. Rather, it provides evidence for the virtues of a more nuanced understanding of patient-centred communication. The article concludes with a discussion of the importance of grounding communication skills training and clinical practice in recordings of actual consultations.