Persistent vegetative state (PVS) is a condition in which a person with severe brain damage is described as being or, more precisely, seeming to be wakeful without awareness. This condition gives rise to many complex ethical and juridical questions, from the moral status of people in this condition and the dignity of their lives to the questions about the possibility of withholding or withdrawing life-supporting medical treatments. People in this condition are regarded as alive and as holding the same rights accorded to every other human being. However, since these people are incompetent, all decisions need to be taken on their behalf. This aspect exemplifies the relational dimension of the question, which involves not only clinicians but also families, people close to the person, and the community as a whole. As for decisions regarding treatments and other wishes, advance directives, although not the same as informed consent expressed in real time, are considered as an important means to reveal one’s wishes in case one might develop this condition and to nominate a surrogate (or proxy) to take decisions on one’s behalf. However, no advance directives were presented in the most important legal cases involving PVS patients around the world; thus, the decision process proved to be extremely difficult. The three main criteria applied in these cases were, firstly, of the substituted judgment, which depends upon the decision of the family or a close person on the basis of the personality of the person in question; secondly, the standard of clear and convincing evidence based on the wishes of the patient expressed while competent; and thirdly, the best interest of the patient. Uncertainties of diagnosis and prognosis of PVS give rise to doubts in addition to uncertainties regarding the methodologies of inferring wishes never expressed by the person. There are also opponents to the withdrawing of life support on principle. The Indian Aruna case highlights also the problem of avoiding the misuse of legal authority to take decisions on behalf of an incompetent person. Since PVS is, typically, a gray area, every solution is destined to be accompanied by a certain degree of doubt.