As patients approach the end of life, their disease process may create an immediate life-threatening emergency, yet invasive interventions may be less likely to provide benefit while carrying the same or greater risks. Knowing when it is time to shift from life-prolonging to more palliative approaches, focused on quality of life and comfort, is emotionally and clinically challenging for patients, families, and physicians. Key factors in the decision process include prognosis, risk-benefit analysis of the proposed intervention, current symptom burden, temporal pattern of the illness, patient's age and life stage, and the patient's goals of care. A structured approach to decision making includes assessing the patient's physical, psychological, and spiritual needs; assessing the patient's support system; discussing prognosis; and assessing patient-specific goals. Physicians can best help patients decide which treatments are appropriate by taking the necessary time to explore all curative and palliative care options, providing honest and timely prognostic information, making clear recommendations, facilitating patient-family discussions, and affirming patient choices.