Dyspnea, the sensation of difficult breathing, is a common debilitating symptom in advanced cancer and chronic progressive cardiopulmonary disease. Primary treatment is correction of the underlying etiology. In incurable illness wherein the cause is irreversible and the goal is palliation, opioids are the drugs of choice for symptomatic relief. This article reviews current knowledge in the pathophysiology of dyspnea, proposed opioid mechanism of action, and evidence of efficacy.