In response to a range of stimuli, neutrophils produce web-like structures known as neutrophil extracellular traps (NETs). The benefits of NETs in pathogen control are commonly offset by excessive release as part of a pro-inflammatory response, as shown in several disorders. The discovery of potential drugs that regulate NET release has helped to enhance our understanding of the role of NETs in immunological protection, inflammatory diseases, and autoimmune disorders. Emerging evidence has indicated that antimicrobials play an immunomodulatory role by influencing the levels of circulating NETs. Herein, we address NETosis in several disorders and detail the mechanisms of NET-mediated damage in infections. We also aim to evaluate recent evidence on the effects of antimicrobials on NET levels. Relevant keywords were searched in PubMed. Studies were evaluated for their relevance, and a narrative review was written accordingly. Several antibiotics, including beta-lactams and cephalosporins, alter NET formation and degradation in a protective manner, resulting in minimal host organ damage. Additionally, some studies have highlighted the immunomodulatory effects of antivirals and antifungals on NET. Further studies are needed to fully understand the clinical implications of NET-antimicrobial interactions and their underlying mechanisms.