Children with acute severe asthma requiring invasive ventilation are among the most difficult to manage in the Intensive Care Unit (ICU). This chapter begins by explaining the pathophysiology of asthma before examining the approaches to its management on the ICU—starting with the evidence for the use of non-invasive ventilation and bronchodilators. Indications for invasive ventilation in acute severe asthma are discussed and important considerations in the conduct of induction of anaesthesia and intubation in this patient group. Ventilation strategies are explored, with particular reference to the concepts of airway resistance, driving pressure, inspiratory flow limitation, and auto-positive end expiratory pressure (PEEP). The use of the mucolytic therapy intratracheal DNAse is discussed, and indications for the use of extracorporeal membrane oxygenation in refractory cases. Finally, the chapter reports on outcomes for children with acute severe asthma and factors associated with higher risk of mortality.