Refractory asthma, especially with a predominance of neutrophils, is a significant clinical challenge. Current treatments, such as corticosteroids, have limited efficacy in controlling inflammation in these patients. Neutrophil extracellular traps (NETs) play a central role in persistent airway inflammation, tissue damage and remodeling in refractory asthma. The review evaluates the preclinical and translational evidence for therapeutic strategies targeting NETs. These strategies include inhibition of NET formation, promotion of their degradation, neutralization of toxic components and enhancement of clearance. Integrating these approaches with precision medicine could improve outcomes in refractory asthma, particularly the neutrophil phenotype. Issues include target specificity, patient heterogeneity, and route of administration.