Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. The latter is likely to contribute significantly to the pathobiology of numerous extrapulmonary effects of the disease--the so-called systemic effects of COPD. The clinical relevance of these systemic effects has been recently recognized; however, many important questions about its pathophysiology remain unanswered. This article reviews what is known about it and, more importantly, highlights what is not (but should be) known in order to stimulate research in this area, in the hope that a better understanding of this field may lead to better treatment options for patients with COPD.