Evaulating patients for living kidney donor transplantation involving a recipient with significant medical issues can create an ethical debate about whether to proceed with surgery. Donors must be informed of the surgical risk to proceed with donating a kidney and their decision must be a voluntary one. A detailed informed consent should be obtained from high-risk living kidney donor transplant recipients as well as donors and family members after the high perioperative risk potential has been explained to them. In addition, family members need to be informed of and acknowledge that a living kidney donor transplant recipient with pretransplant extrarenal morbidity has a higher risk of a serious adverse outcome event such as graft failure or recipient death. We review 2 cases involving living kidney donor transplant recipients with significant comorbidity and discuss ethical considerations, donor risk, and the need for an extended informed consent.