Drotrecogin alfa has been shown to reduce mortality in severe sepsis. However, it remains unlicensed for use in patients with previous liver transplantation. We report its use in such a case. Prior to administration a risk benefit analysis was performed in line with General Medical Council recommendations. This included being satisfied that no appropriately licensed alternative would better serve the patient's needs and that sufficient evidence existed to demonstrate the safety and efficacy of the drug. Responsibility was taken for prescription, monitoring and follow up. The process was carefully documented and the patient recovered fully with no adverse effects. To date the only published data on the use of drotrecogin alpha in transplant recipients is a case series of three patients. Further published data may encourage review of the licence.