Background: In the Netherlands physicians are allowed to grant requests for euthanasia or physician-assisted suicide (EAS) if they meet several requirements of due care. According to jurisprudence, a physician is not allowed to end the life of a patient whose request for EAS is based on being ‘tired of living’, because such a request falls outside the medical domain. Our previous studies have shown that in spite of this, such requests are made approximately 400 times a year. Objectives: To learn more about patients who request EAS because they are tired of living, and about factors that influence the decision of the physician. Design: Questionnaires ( n = 4842) completed by general practitioners ( n = 3994). Results: According to the physicians, 17% of patients who requested EAS were ‘tired of living’. Of 139 patients in whose request for EAS being tired of living played a major role, 47% suffered from cancer, 25% suffered from another severe disease and 28% had no severe disease. In all three groups the same three symptoms occurred most frequently, ‘feeling bad’, ‘tired’, and ‘not active’. Each of these symptoms occurred in more than half of the patients in each group. Most of the requests from patients with cancer were granted, but those from patients who had some other severe disease, or no severe disease at all, were refused. Factors that were related to granting a request were: the presence of unbearable and hopeless suffering, the absence of alternatives, and the absence of depressive symptoms. Conclusions: Being tired of living can play a major role in requests for EAS, both in the absence and the presence of a severe disease. The high occurrence of symptoms in the absence of a classifiable severe disease implies that physical symptoms are prevalent in this group of patients, leaving the legal requirement for EAS of ‘a medical cause’ open to interpretation in the more complex medical practice.