This chapter provides an in-depth review of airway secretion clearance techniques and cough augmentation methods in mechanically ventilated patients, emphasizing the role these techniques play in weaning and extubation. It examines the impact of common airway clearance mechanisms, such as mucociliary transport and cough, which are often impaired in critically ill patients due to artificial airways, reduced mobility, and weak respiratory muscles. Various methods to aid secretion clearance are discussed, including ventilator hyperinflation, expiratory rib cage compression (ERCC), PEEP-ZEEP maneuvers, and mechanical insufflation-exsufflation (MI-E). Optimizing the ratio between peak inspiratory and expiratory flow (PIF-PEF) for effective mucus transport is highlighted as a crucial factor for improving respiratory function and reducing extubation failure risk. Additionally, the relationship between cough strength, often measured by cough peak flow (CPF), and extubation success is emphasized. A CPF of 55–65 L/min is identified as a threshold indicative of successful extubation. Interventions such as manually assisted coughing and MI-E are highlighted for their effectiveness in boosting cough strength, particularly in patients with neuromuscular weakness or at risk of secretion retention. Practical guidelines for implementing these techniques are provided to optimize secretion clearance and enhance the chances of successful extubation in critically ill patients.