Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome encompassing the clinical presentations of chronic bronchitis and emphysema. Moderate-to-severe COPD is estimated to affect 80 million people worldwide. The diagnosis of COPD is made using spirometry, demonstrating the presence of obstruction that does not completely reverse with the administration of an inhaled bronchodilator. Treatment of COPD is titrated to severity, and in stage II–IV disease, combinations of different classes of bronchodilators, and bronchodilator and anti-inflammatory combinations, are recommended. Treatment of COPD is multimodal, including pharmacologic therapy, long-term oxygen therapy, smoking cessation, cardiopulmonary rehabilitation (including breathing retraining) and disease education. This article focuses on pharmacologic therapies, and more specifically the evidence for combination pharmacologic therapy that has emerged over the past few years. Prominent human clinical trials are reviewed and results are summarized with a focus on the steps required to change clinical practice. Finally, a perspective on future changes in the field of COPD pharmacotherapy is provided in light of recent changes.