Mucus plugging (MP) plays a crucial role in asthma as it is involved in airflow obstruction, inflammation, and airway remodelling mechanisms. Advances in imaging techniques, such as high-resolution chest CT and hyperpolarised gas MRI, have improved the assessment of MP, linking its burden to disease severity and treatment response. While these radiological modalities provide valuable insight into mucus obstruction, their routine application in clinical practice remains limited. Similarly, novel inflammatory biomarkers have emerged as promising tools for evaluating airway mucus, though their clinical use requires further validation. Mucus-targeting treatments, including biologics that target inflammatory pathways, mucolytics and airway clearance techniques, have shown promising effects. A personalised approach, integrating diagnostic tools, functional evaluation and targeted therapies, is key to mitigating the impact of MP. Clinical case studies demonstrate the complexity of MP pathophysiology and the need for tailored interventions to optimise outcome. Further understanding of polysaccharide biology, the biophysical properties of hydrogels, mucus hydration, epithelial ion transport and mucociliary clearance mechanisms is necessary to improve therapies for MP.