Chronic obstructive pulmonary disease (COPD) is a respiratory syndrome affecting more than 80 million people worldwide and is estimated to become the third-leading cause of death worldwide by 2030. A standard-of-care approach to COPD treatment is multifaceted, including pharmacological and non-pharmacological therapies, yet the optimum combination among many bronchodilator possibilities remains unclear. We discuss the evidence for effectiveness of combination bronchodilator and inhaled corticosteroid therapy in affecting the minimal clinically important difference for these agents in COPD. We propose an approach to the rational use of these combinations that favours the combination of long-acting β-adrenergic agents with long-acting anticholinergic agents in lieu of any other bronchodilators whenever possible. We suggest that, to better detect effects of disease modification in COPD, future studies of combination bronchodilator effectiveness should emphasize endpoints other than short-term change in post-bronchodilator forced expiratory volume in 1 second (FEV(1)).