Despite significant advances in treatment, chronic obstructive pulmonary disease (COPD) remains a chronic and progressive disease that frequently leads to premature mortality. COPD is associated with a constellation of significant symptoms, including dyspnea, cough, wheezing, pain, fatigue, anxiety, depression, and insomnia, and is associated with increased morbidity. Palliative care is appropriate to support these patients. However, historically, palliative care has focused on supporting patients with malignant disease, rather than progressive chronic diseases such as COPD. Therapies for COPD often result in functional and symptomatic improvements, including health-related quality of life (HRQL), and palliative care may further improve symptoms and HRQL. Provision of usual palliative care therapies for this patient population requires understanding the pathogenesis of COPD and common disease-targeted pharmacotherapies, as well as an approach to balancing life-prolonging and HRQL care strategies. This review describes COPD and current targeted therapies and their effects on symptoms, exercise tolerance, HRQL, and survival. It is important to note that medications commonly used for symptom management in palliative care can interact with COPD medications resulting in increased risk of adverse effects, enhanced toxicity, or changes in clearance of medications. To address this, we review pharmacologic interactions with and precautions related to use of COPD therapies in conjunction with commonly used palliative care medications. Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.