Mike Thomas,1 David MG Halpin,2 Marc Miravitlles3 1Primary Care and Population Sciences, University of Southampton, Southampton, 2Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 3Pneumology Department, Hospital Universitari Vall d’Hebron, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Spain Abstract: Inhaled bronchodilator medications are central to the management of COPD and are frequently given on a regular basis to prevent or reduce symptoms. While short-acting bronchodilators are a treatment option for people with relatively few COPD symptoms and at low risk of exacerbations, for the majority of patients with significant breathlessness at the time of diagnosis, long-acting bronchodilators may be required. Dual bronchodilation with a long-acting β2-agonist and long-acting muscarinic antagonist may be more effective treatment for some of these patients, with the aim of improving symptoms. This combination may also reduce the rate of exacerbations compared with a bronchodilator-inhaled corticosteroid combination in those with a history of exacerbations. However, there is currently a lack of guidance on clinical indicators suggesting which patients should step up from mono- to dual bronchodilation. In this article, we discuss a number of clinical indicators that could prompt a patient and physician to consider treatment escalation, while being mindful of the need to avoid unnecessary polypharmacy. These indicators include insufficient symptomatic response, a sustained increased requirement for rescue medication, suboptimal 24-hour symptom control, deteriorating symptoms, the occurrence of exacerbations, COPD-related hospitalization, and reductions in lung function. Future research is required to provide a better understanding of the optimal timing and benefits of treatment escalation and to identify the appropriate tools to inform this decision. Keywords: COPD, dual bronchodilation, monobronchodilation, ICS, triple therapy