Opioids have been used for many years to relieve breathlessness in patients with advanced COPD. They may possess several mechanisms by which they relieve dyspnea, both peripheral and central in origin. At the same time, their systemic use for this purpose gives rise to a concern about respiratory depression. Morphine also may be administered by the inhalational route to relieve breathlessness without inducing side effects that might be encountered if given systemically. In this issue of CHEST (see page 691), Foral and colleagues reviewed seven studies in patients with a variety of cardiorespiratory disorders who received nebulized morphine and whose dyspnea responses were subsequently assessed. Five of the studies were conducted in patients with COPD, while another study evaluated a mix of pulmonary and nonpulmonary patients, and the seventh studied a small cohort of patients with interstitial lung disease (ILD). All but one of the studies were prospective and double-blinded. Five studies were crossover in design, and only four studies (three in COPD patients) made use of placebos. In some studies, dyspnea was evaluated by means of a modified Borg scale or visual analog scale (VAS) during exercise. The authors’ conclusion was that the evidence did not support the use of nebulized morphine for the relief of dyspnea or in the improvement of exercise tolerance in patients with COPD or ILD. They recognized that differences in dose, differences in administration schedule, and inconsistent use of oxygen and bronchodilators could have contributed to the variability in results. In addition, all the prospective studies evaluated small numbers of patients (range, 6 to 16 patients). The retrospective investigation assessed 54 patients with different diagnoses. Most studies used morphine sulfate as the opiate, while another used glucuronide or chlorohydrate salt. In some studies, bronchodilators were administered before the morphine was nebulized. The doses and frequency of morphine use varied widely among the studies. Cumulatively, side effects were few and mild.