To care for patients at the end of life, family physicians should be able to evaluate the causes of symptoms, differentiate between distressing symptoms and common end-of-life changes, and balance treatment effectiveness with potential adverse effects, while ensuring alignment with the patient's values and wishes. For severe pain and dyspnea, opioids are the mainstay of treatment. Palliation of pain with adjuvant medications and nonpharmacologic measures may delay or decrease the need for opioids. Nausea can be treated by reducing exacerbating factors and choosing agents that target the specific receptor site affected. Constipation should be prevented or treated quickly with osmotic and stimulant laxatives. Severe opioid-induced constipation may require enemas, prokinetics, or mu-opioid antagonists. Anorexia is extremely common at the end of life and may not warrant specific treatment in the absence of distress. Appetite stimulants can be considered after dysphagia, dyspepsia, nausea, and constipation are addressed. Early recognition of delirium, reduction of offending medications, and frequent reorientation may reduce the need for psychotropic medications. Mood disturbances should be distinguished from grief and cognitive loss, and treatment should consider prognosis and time to benefit.