Chronic obstructive pulmonary disease (COPD) continues to be associated with increased morbidity and mortality risk in spite of updated guidelines and a better understanding of this condition. Progressive airflow limitation and resultant hyperinflation-the respiratory hallmarks of this complex and often under-diagnosed disease-can be treated with pharmacotherapies emitted via nebulizers, pressurized metered-dose inhalers, dry powder inhalers, or a Soft Mist inhaler. Pharmaceutical company proprietary issues, technological innovations, and societal pressure have expanded the list of available inhalers, with a limited range of medications available for any one device. Each device has different operating and maintenance instructions, and successful use of a given drug/device combination requires that patients understand, maintain, and use each of their devices properly in order to ensure consistent and optimal pulmonary drug delivery. Clinicians are faced with a range of physical and psychosocial issues unique to each patient with COPD that must be overcome in order to match a suitable inhaler to the individual. Improved drug delivery afforded by next-generation inhalers, coupled with an awareness of device-specific and patient-specific variables affecting inhaler use, may improve clinical outcomes in the treatment of COPD.