Although mixed infections are known to be clinically relevant in conditions such as nosocomial pneumonia and ventilator-related pneumonia, it is increasingly recognized that a substantial number of community-acquired lower respiratory tract infections may also be attributed to more than one pathogenic organism. A better definition of the true incidence of mixed infections in community-acquired lower respiratory tract infections is partly derived from recent advances in available diagnostic methods (eg, molecular biology). Two points still must be determined: whether the presence of a mixed infection is associated with altered outcomes and whether empirical antibiotic selection should be modified to account for potential polymicrobial infections.