Breakthrough bleeding is a common problem in postmenopausal women taking hormone replacement therapy (HRT) and is often the single most important factor deterring women from continuing to use HRT, or from starting it in the first place. The mechanisms which underlie this unscheduled bleeding are poorly understood. The benefits of HRT in terms of longevity and quality of life are becoming increasingly apparent, and a greater understanding of why this bleeding occurs and how we can prevent or treat it, will undoubtedly enable more women to reap the potential considerable benefits of long-term oestrogen and progestogen replacement. What sets postmenopausal women apart from their counterparts in the mid-reproductive years is the increased likelihood of endometrial adenocarcinoma in which unscheduled bleeding is the presenting symptom. Therefore, spontaneous postmenopausal bleeding must always be appropriately evaluated. Hence, the occurrence of unscheduled bleeding with HRT may provide a dilemma with diagnosis as well as a challenge to acceptability. Combined HRT regimens tend to be predominantly progestogenic, and there is increasing evidence to suggest that some of the vascular changes seen in women taking long-term, low-dose progestogen-only contraceptives may also occur in women taking HRT.