This is the case report of an 80-year-old woman with advanced chronic obstructive pulmonary disease (COPD), multimorbidity and frailty. Despite regular critical re-evaluation of on-going medication, a significant reduction of prescribed medication was not achieved up until the patient’s terminal phase, and this may have contributed to several episodes of delirium. It was particularly difficult to reduce the number of prescribed drugs due to cardiovascular, endocrinologic, orthopaedic, neurologic, psychiatric and pulmonary comorbidities. Probable drug–drug interactions and side effects were repeatedly observed. This case report aims to describe a dilemma frequently encountered in the care of patients with progressed pulmonary disease in the context of frailty and multimorbidity.