As many as 10 million Americans have chronic obstructive pulmonary disease and as a consequence experience disabling symptoms, high cost of care, and substantial mortality. Several new approaches are being investigated for possible benefit in managing (or even reversing) chronic obstructive pulmonary disease. This article reviews 4 new approaches that are either in or close to phase III trials: long-acting bronchodilators, phosphodiesterase-4 inhibitors, vasodilators, and retinoids. Of those tiotropium appears to be the closest to receiving clinical approval in the United States. The risk/benefit ratio and the cost-effectiveness of the other compounds are less clear and await additional study.