OBJECTIVE: To describe the etiologies and indicators of weaning failure and to provide a framework for planning interventions to facilitate weaning of long-term ventilation patients. DATA SOURCE: A Medline search of human studies in English on weaning from mechanical ventilation. ARTICLE SELECTION: Articles were selected if they pertained to the assessment and management of weaning failure. Both research and review articles were included. DATA EXTRACTION: All pertinent articles were described, along with their limitations. DATA SYNTHESIS: Weaning from mechanical ventilation is an emerging science. Caring for patients who are difficult to wean requires expert clinical decision making so patients do not feel defeated and have the best chances for success. Combining the limited research on weaning intervention with clinical expertise helps to build a scientific basis for care and can assist clinicians in tailoring interventions to specific problems that precipitate weaning failure. CONCLUSION: A scientific approach to care may promote weaning in difficult cases and provide directions for future research into the etiologies of weaning failure.