Especially relevant, however, is that an important component of COPD treatment involves modulation of autonomic tone, either by β-adrenergic receptor activation or by vagal inhibition. While the symptomatic benefits of these interventions apply in the context of lung function, current therapeutic formulations do not reduce mortality and moreover cause significant systemic side effects, particularly on the heart. Alternative approaches to treatment of COPD (for example the use of β-blockade) currently seem inappropriate, but perhaps no more so than β-blockade for heart failure might have seemed 20 years ago. Indeed, chronic cardioselective β-blockade is remarkable well tolerated.73 Currently, little is known about the effect of such treatments on neurohumoral activation and COPD. But as this aspect of COPD becomes better understood, and as pharmaceuticals become more target specific, new insights may direct novel therapeutic approaches. However, albeit data supporting this proposal are available, we have to acknowledge that they are limited. Randomized controlled trials investigating measurable end points such as sympathetic activation, quality of life, lung function, hospital admissions, and mortality are thus needed.