New brain-computer interface and neuroimaging techniques are making differentiation less ambiguous and more accurate between unresponsive wakefulness syndrome patients and patients with higher cognitive function and awareness. As research into these areas continues to progress, new ethical issues will face physicians of patients suffering from total locked-in syndrome (total LIS), characterized by complete loss of voluntary muscle control, with retention of cognitive function and awareness detectable only with neuroimaging and brain-computer interfaces. Physicians, researchers, ethicists and hospital ethics committees should be aware of and prepared to handle ethical issues unique to these totally locked-in patients. Several thought experiments are discussed, to highlight potential ethical dilemmas surrounding surrogate decision-making, autonomy, end-of-life care, and pediatric care, which will be unique to total LIS patients. These, along with other ethical problems especially relevant to total LIS patients, merit further discussion among physicians, researchers, ethicists and hospital ethics committees, to facilitate consensus regarding these issues, and improve patient care.