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Non-resectable colorectal liver metastases (CLMs) are generally considered an absolute contraindication for liver transplantation. However, a 2013 Norwegian study transplanted livers in 21 patients with CLMs and reported excellent outcomes. The current article reports on the deliberations of the Wits Human Research Ethics Committee (Medical), which resulted in approval of the first liver transplant for a patient with CLMs in South Africa (SA). Factors considered included the scarcity of donor organs in SA, weighing the best interests of different groups of patients and the requirement for extensive and careful information provision. Originally under the auspices of Section 37 of the World Medical Association Declaration of Helsinki (2013), the protocol has now been formalised as a research project.