The article discusses the potential benefits of combining macrolides with β-lactam antibiotics in the treatment of severe community-acquired pneumonia (CAP). Recent observational studies suggest that adding a macrolide to standard antibiotic therapy may reduce mortality in critically ill patients with CAP. The authors highlight the pleiotropic effects of macrolides, including their ability to inhibit bacterial quorum sensing, which could be a key mechanism of action in severe infections. Quorum sensing is a bacterial cell-to-cell communication process that regulates gene expression, biofilm formation, and virulence. Macrolides have been shown to antagonize quorum sensing in *Pseudomonas aeruginosa*, reducing virulence and biofilm formation. The article also explores the immunomodulatory effects of macrolides, which could contribute to their therapeutic benefits. However, the authors emphasize the need for a large randomized controlled trial to confirm the survival advantage of macrolide combinations over other antibiotic combinations. The article concludes by highlighting the potential of quorum sensing as a novel target for the development of new anti-infective drugs.The article discusses the potential benefits of combining macrolides with β-lactam antibiotics in the treatment of severe community-acquired pneumonia (CAP). Recent observational studies suggest that adding a macrolide to standard antibiotic therapy may reduce mortality in critically ill patients with CAP. The authors highlight the pleiotropic effects of macrolides, including their ability to inhibit bacterial quorum sensing, which could be a key mechanism of action in severe infections. Quorum sensing is a bacterial cell-to-cell communication process that regulates gene expression, biofilm formation, and virulence. Macrolides have been shown to antagonize quorum sensing in *Pseudomonas aeruginosa*, reducing virulence and biofilm formation. The article also explores the immunomodulatory effects of macrolides, which could contribute to their therapeutic benefits. However, the authors emphasize the need for a large randomized controlled trial to confirm the survival advantage of macrolide combinations over other antibiotic combinations. The article concludes by highlighting the potential of quorum sensing as a novel target for the development of new anti-infective drugs.