The onset of agitation and distress in a mechanically ventilated patient should initiate a careful assessment that considers whether there has been progression of the underlying disease, a new medical complication, or adverse effects from medical interventions and procedures, including intubation and mechanical ventilation. This article focuses on problems that relate to mechanical ventilation and the interactions of the "patient-ventilator system". The authors suggest an initial approach to the patient who develops respiratory distress, and then review the appropriate indications for sedative and paralytic medications.