Despite the availability of excellent antibiotics, the mortality from community-acquired pneumonia (CAP) remains substantial. Most deaths occur during the first week of hospitalization. Because antibiotics rapidly eradicate bacteria from pulmonary secretions, an ongoing inflammatory response may be responsible for the poor outcome, and treatment with immunomodulatory drugs might be beneficial in this setting. Macrolides and statins exert a broad range of anti-inflammatory effects. Although randomized control trials have not been done, clinical evidence favors the addition of a macrolide to a beta-lactam for the treatment of pneumococcal pneumonia and supports a role for macrolides in the treatment of all-cause CAP without regard to their anti-microbial activity. The weight of several retrospective studies suggests that statins be considered in treating acute CAP. Further support for the use of statins derives from the high association between pneumonia and acute myocardial infarction. Aspirin might also be of benefit in treating patients hospitalized for pneumonia because of its anti-inflammatory activity as well as its benefits in acute myocardial infarction. Treatment of CAP with corticosteroids has yielded mixed results and the value of this approach is not well established, although further research is currently underway. Ibuprofen is not of benefit in treating sepsis in humans and glitazones may increase the risk of severe pneumonia.