Successful ventilator weaning requires adequate respiratory muscle strength, gas exchange capability, and absence of factors that increase ventilatory demand. The diaphragm, the primary muscle of inspiration, generates 60-80% of tidal volume. Mechanical ventilation causes ventilator-induced diaphragmatic dysfunction (VIDD) through diaphragmatic disuse atrophy, occurring within 18-69 hours of controlled mechanical ventilation through proteolytic pathways (calpain and caspase-3 activation). Critical illness polyneuromyopathy further impairs respiratory muscle function. The rapid shallow breathing index (RSBI = respiratory rate / tidal volume in liters) is the most validated weaning predictor: RSBI <105 predicts successful weaning with 97% sensitivity. Spontaneous breathing trials (SBT) assess the patient's ability to breathe independently using either T-piece (complete ventilator disconnection), CPAP (5 cmH2O), or pressure support (5-8 cmH2O) for 30-120 minutes. Weaning failure occurs in 20-30% of patients, most commonly from cardiac dysfunction (increased preload from negative intrathoracic pressure), respiratory muscle weakness, or excessive respiratory load.