Mechanically ventilated patients with chronic obstructive pulmonary disease often prove challenging to the clinician due to the complex pathophysiology of the disease and the high risk of patient-ventilator asynchrony. These problems are encountered in both intubated patients and those ventilated with noninvasive ventilation. Much knowledge has been gained over the years in our understanding of the mechanisms underlying the difficult interaction between these patients and the machines used to provide them with the ventilatory support they often require for prolonged periods. This paper attempts to summarize the various key issues of patient-ventilator interaction during pressure support ventilation, the most often used partial ventilatory support mode, and to draw clinicians' attention to the need for sufficient knowledge when setting the ventilator at the bedside, given the often conflicting goals that must be met.