A new article published in the Expert Review of Respiratory Medicine reported on the recent international recommendations for the treatment of chronic obstructive pulmonary disease (COPD), which suggest that N-Acetyl-l-cysteine (NAC) reduces acute exacerbation of COPD (AECOPD) with a modest improvement in the patient’s health status, owing to its mucolytic activity. Additionally, NAC also has anti-infective properties and specific antioxidant and anti-inflammatory effects in the airways. It was discussed that the protective effect of NAC against AECOPD is related not only to its well-documented mucolytic activity but also to the activation of antioxidant pathways, inhibition of pro-oxidant and inflammatory pathways, and modulation of human bronchial tone. It was stated that mucolytic, anti-infective, anti-inflammatory, as well as antioxidant actions of the drug are beneficial in patients with AECOPD.