Chronic obstructive pulmonary disease presents with different phenotypes. While patients with pulmonary emphysema and hyperinflation are treated with lung volume reduction therapies, new treatment options are available for patients suffering mainly from chronic bronchitis and COPD exacerbations. Targeted lung denervation aims to ablate the parasympathetic fibers of the vagus nerve with radiofrequency energy, in order to reduce bronchoconstriction and exacerbations. Bronchial rheoplasty and spray cryotherapy both target patients with symptoms of chronic bronchitis. While bronchial rheoplasty uses nonthermal, pulsed electrical energy to ablate the goblet cells, spray cryotherapy induces fresh-freezing of the goblet cells by delivering a precise thermal dose of liquid nitrogen at −196 °C to the lung. Both procedures aim to reduce goblet cell hyperplasia and thereby sputum overproduction and improve quality of life. These innovative new treatment options are still under investigation but have shown promising results in recent trials in patients with persistent symptoms despite optimal medical therapy. Careful patient selection is key to successful therapy. Further studies are needed before implementation of these therapies in routine clinical practice.