Mechanical ventilation (MV) is an essential part of modern intensive care medicine. MV is performed in patients with severe respiratory failure caused by insufficiency of the respiratory muscles and/or lung parenchymal disease when/after other treatments, i. e. oxygen, body position, secretion management, medication or non invasive ventilation have failed.In the majority of ICU patients weaning is routine and does not present any problems. Nevertheless 40-50 % of the time during mechanical ventilation is spent on weaning. About 20 % of patients need continued MV despite resolution of the conditions which originally precipitated the need for MV.There maybe a combination of reasons; chronic lung disease, comorbidities, age and conditions acquired in ICU (critical care neuromyopathy, psychological problems). According to an International Consensus Conference the criteria for "prolonged weaning" are fulfilled if patients fail at least three weaning attempts or require more than 7 days of weaning after the first spontaneous breathing trial. Prolonged weaning is a challenge. An inter- and multi-disciplinary approach is essential for weaning success. Complex, difficult to wean patients who fulfill the criteria for "prolonged weaning" can still be successfully weaned in specialised weaning units in about 50% of cases.In patients with unsuccessful weaning, invasive mechanical ventilation has to be arranged either at home or in a long term care facility.This S2-guideline was developed because of the growing number of patients requiring prolonged weaning. It is an initiative of the German Respiratory Society (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V., DGP) in cooperation with other societies engaged in the field.The guideline is based on a systematic literature review of other guidelines, the Cochrane Library and PubMed.The consensus project was chaired by the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) based on a formal interdisciplinary process applying the Delphi-concept. The guideline covers the following topics: Definitions, epidemiology, weaning categories, pathophysiology, the spectrum of treatment strategies, the weaning unit, discharge from hospital on MV and recommendations for end of life decisions. Special issues relating to paediatric patients were considered at the end of each chapter.The target audience for this guideline are intensivists, pneumologists, anesthesiologists, internists, cardiologists, surgeons, neurologists, pediatricians, geriatricians, palliative care clinicians, nurses, physiotherapists, respiratory therapists, ventilator manufacturers.The aim of the guideline is to disseminate current knowledge about prolonged weaning to all interested parties. Because there is a lack of clinical research data in this field the guideline is mainly based on expert opinion.