Chronic obstructive pulmonary disease (COPD) no longer is regarded simply as a disease of the lungs and airways. There is growing awareness of the multisystemic nature of this disease. Research has shown increased levels of systemic inflammation and cardiovascular, neurologic, psychiatric, and endocrine system dysfunction associated with COPD. Skeletal muscle dysfunction associated with COPD is discussed in the article by Schols in this issue of Clinics in Chest Medicine. In this article, other systemic manifestations of COPD are discussed. Although this field is expanding rapidly, this article focuses on recent advances and reviews.