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Treatment for chronic breathlessness should be considered only when management of the underlying disease has been fully optimized. Opioids are indicated as first-line therapy, as this is the only class of drugs that has demonstrated clear clinical benefits in patients with chronic refractory breathlessness. Oral and parenteral, but not nebulized, delivery of opioids has been shown to be effective. Data plainly indicating that benzodiazepines or oxygen have therapeutic benefits in treating this condition are currently lacking.