Although many investigators have attempted to identify weaning predictors and weaning modes for use in long-term mechanically ventilated patients, none has emerged as superior. Furthermore, few investigators have viewed the process of weaning as a dynamic continuum; thus, guidelines for care of these patients have yet to be developed. Facilitative methods and therapies to enhance weaning potential, although attractive, have little scientific basis for application. Care delivery systems, which focus on systematic, comprehensive and coordinated care, are promising because outcomes demonstrate that they are economical, safe, and effective. This article reviews the research on weaning adult, long-term mechanically ventilated patients, suggests future research directions, and highlights the scientific basis for practice guidelines.