Macrolides are being considered as a potential treatment for community-acquired pneumonia (CAP), with recent studies suggesting that adding a macrolide to a β-lactam antibiotic may improve survival. This is due to the pleiotropic effects of macrolides, including their ability to inhibit bacterial quorum sensing, which is a form of cell-to-cell communication that influences bacterial virulence and biofilm formation. Quorum sensing is important in the pathogenesis of several pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Macrolides at subminimum inhibitory concentrations have been shown to inhibit quorum sensing in P. aeruginosa, reducing virulence and biofilm formation. This could explain why macrolides may be beneficial in severe CAP, as they may reduce bacterial pathogenicity and improve outcomes. Several studies have shown that macrolide combination therapy with β-lactams is associated with reduced mortality in critically ill patients with CAP. A recent observational study found that patients receiving macrolide combination therapy had a lower mortality rate compared to those receiving fluoroquinolone therapy. However, the data are not yet sufficient to confirm the survival advantage of macrolides in CAP. A large randomized controlled trial is needed to determine the true efficacy of macrolides in this setting. In addition to their antibacterial effects, macrolides have immunomodulatory properties. They can alter cytokine and chemokine production, reduce cellular infiltration, and decrease mucus production. These effects may contribute to the improved outcomes seen with macrolide therapy. Macrolides are also being explored for their potential in treating a wide range of pulmonary and extrapulmonary conditions, including asthma, cystic fibrosis, rhinosinusitis, inflammatory bowel disease, psoriasis, and rosacea. The role of quorum sensing in bacterial pathogenesis is increasingly recognized, and targeting this pathway may offer a new approach to the treatment of infections. Macrolides, by inhibiting quorum sensing, may provide a novel mechanism for reducing mortality in CAP. Further research is needed to fully understand the role of quorum sensing in CAP and to determine the optimal use of macrolides in this setting.Macrolides are being considered as a potential treatment for community-acquired pneumonia (CAP), with recent studies suggesting that adding a macrolide to a β-lactam antibiotic may improve survival. This is due to the pleiotropic effects of macrolides, including their ability to inhibit bacterial quorum sensing, which is a form of cell-to-cell communication that influences bacterial virulence and biofilm formation. Quorum sensing is important in the pathogenesis of several pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Macrolides at subminimum inhibitory concentrations have been shown to inhibit quorum sensing in P. aeruginosa, reducing virulence and biofilm formation. This could explain why macrolides may be beneficial in severe CAP, as they may reduce bacterial pathogenicity and improve outcomes. Several studies have shown that macrolide combination therapy with β-lactams is associated with reduced mortality in critically ill patients with CAP. A recent observational study found that patients receiving macrolide combination therapy had a lower mortality rate compared to those receiving fluoroquinolone therapy. However, the data are not yet sufficient to confirm the survival advantage of macrolides in CAP. A large randomized controlled trial is needed to determine the true efficacy of macrolides in this setting. In addition to their antibacterial effects, macrolides have immunomodulatory properties. They can alter cytokine and chemokine production, reduce cellular infiltration, and decrease mucus production. These effects may contribute to the improved outcomes seen with macrolide therapy. Macrolides are also being explored for their potential in treating a wide range of pulmonary and extrapulmonary conditions, including asthma, cystic fibrosis, rhinosinusitis, inflammatory bowel disease, psoriasis, and rosacea. The role of quorum sensing in bacterial pathogenesis is increasingly recognized, and targeting this pathway may offer a new approach to the treatment of infections. Macrolides, by inhibiting quorum sensing, may provide a novel mechanism for reducing mortality in CAP. Further research is needed to fully understand the role of quorum sensing in CAP and to determine the optimal use of macrolides in this setting.