By definition, chronic obstructive pulmonary disease (COPD) is associated with an abnormal inflammatory response of affected lungs. Therefore, the search for an effective anti-inflammatory therapy for this debilitating disease is intense. However, to date, there is no such anti-inflammatory treatment for COPD. While there are some modest effects of inhaled corticosteroids on selected clinical endpoints in COPD, it remains to be proven that the observed effects are due to changes in the underlying inflammation, in particular since relevant clinical endpoints of COPD can be significantly improved by treatments not targeting inflammation. Therefore, it appears justified to reconsider the present knowledge about any linkage of local and systemic inflammation and clinical features of COPD, including lung function, exacerbations, disease progression, and mortality. Any such link needs to be carefully established before future anti-inflammatory therapies for COPD are developed and investigated in clinical trials, in particular since proof-of-concept trials aiming merely at inflammatory markers in COPD may not be predictive of clinical success or failure. The present review summarizes current knowledge about the role of inflammation in COPD, and critically analyzes results from clinical trials with inhaled corticosteroids and phosphodiesterase-4 inhibitors in COPD, the two classes of putative antiinflammatory agents with the richest body of evidence from controlled studies.