Recent data have indicated that hormone replacement therapy (HRT) is associated with an increased risk of venous thrombo-embolism. Although the relative risk is significantly higher, the absolute risk remains small. Epidemiological studies on which the increased risk was based may have been open to biases, including those of referral, investigation and diagnosis. None the less, the association appears real albeit the mechanism poorly understood. Potential mechanisms include unmasking of an underlying thrombophilia or combination with other recognized risk factors for venous thrombo-embolism. The implications of these findings have to be placed firmly in the clinical context and weighed against the established benefits of hormone replacement therapy, including relief of menopausal symptoms, prevention of osteoporosis and arterial-vascular disease. Patients with a personal or family history of venous thrombo-embolism should be screened for underlying thrombophilia and such screening may be extended to relatives. However, the risk of venous thrombo-embolism following initiation of HRT is not yet known. None the less, HRT should be used with caution in this situation and may be best avoided, unless associated with concomitant antithrombotic therapy, in certain thrombophilias, expert advice should be sought. Patients without risk factors should be advised of the small increase in risk of venous thrombosis which is greatest during the first year. Where additional risk factors are present the situation will have to be assessed on an individual basis for each patient. For example, the beneficial effects of HRT in an obese patient at risk of arterial disease may outweigh the small risk of thrombosis. Patients already on HRT should have some assessment of the risk of venous thrombosis made and where there are features suggestive of thrombophilia screening performed.