Increasingly, patients with pituitary disease are evaluated and treated at cancer centers. In many ways, these patients resemble patients with other malignant brain tumors. Although the majority of pituitary adenomas are benign, the physical, emotional, and cognitive changes that these patients experience on their well-being is malignant. Pituitary disease causes a variety of physical illnesses resulting from the alterations in the hypothalamic-pituitary-end organ axis. In addition, patients with pituitary diseases may experience many emotional problems, including depression, anxiety, behavioral disturbances, and personality changes, above and beyond the many reactions these patients may have to the myriad of adjustments that they must make in their lives. There is a growing understanding that pituitary patients may experience these emotional problems as a result of long-term effects that the pituitary tumor itself, treatment, and/or hormonal changes have on the hypothalamic-pituitary-end organ axis. The authors present a series of cases, in which patients with pituitary disease were diagnosed and treated for depression and showed little response to the treatment for depression. When the diagnosis of apathy syndrome was considered and treatment implemented, the patients' condition improved. A review of the literature on apathy, hypothalamic-pituitary-end organ axis dysfunction, and treatment for apathy syndrome is included.