Biofilm formation is a key factor in the persistence and recurrence of otorhinolaryngology (ORL) infections, driving antimicrobial resistance and treatment failure. Chronic conditions, such as rhinosinusitis, otitis media and tonsillitis, are linked to biofilm-producing pathogens, forming protective extracellular matrices that shield bacteria from immune defenses and antibiotics. The present review explores emerging pharmacological strategies to disrupt biofilm integrity and improve treatment outcomes. Strategies such as quorum sensing inhibitors, antibiofilm peptides, enzymatic dispersal agents, and drug repurposing can potentially disrupt biofilms and counter-resistance mechanisms. Furthermore, novel therapies (including nanotechnology-based drug delivery systems, phage therapy and immunomodulation) offer innovative alternatives for managing biofilm-associated infections. However, clinical implementation remains challenging. Future research should prioritize optimizing drug formulations, refining delivery techniques, and exploring synergistic combinations to enhance biofilm eradication. Implementing these innovative strategies can improve the management of chronic ORL infections, reducing recurrence rates and enhancing patient outcomes.