Weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD) or left ventricular failure may be difficult. At the time of intubation and initiation of mechanical ventilatory support, this treatment is usually life-saving in the short term. Only later on, the condition which necessitated such support may prove irreversible. COPD patients often require positive end-expiratory pressure to enable them to trigger the ventilator comfortably. Patients with left ventricular failure need pharmacological support to reduce the circulating volume and to reduce left ventricular afterload because the ventilatory support itself reduces both left ventricular preload and afterload. Gradual withdrawal of pressure support and gradually increasing periods of T-piece weaning are probably equally effective. New methods have been described but have not yet been tested in randomized controlled trials. More important than the method of weaning is the presence of qualified and dedicated nursing support. Not all patients can be weaned; for most of those who cannot, prospects are grim. These patients require optimal palliative support with recognition of their autonomy.