The development of weaning failure and need for PMV is multifactorial in origin, involving disorders of pulmonary mechanics and complications associated with critical illness. The underlying disease process is clearly important when discussing mechanisms of ventilator dependence; interventions therefore must be tailored to individual patients. Unfortunately, the main conclusion that can be drawn from the sum of the studies investigating patients on PMV to date is that an evidence-based approach to weaning is not possible and more research needs to be done. New studies need to incorporate severity-of-illness scores and an assessment of principal and comorbid conditions to allow for comparison of the findings from different centers. The best approach to a patient requiring PMV after exclusion of easily treatable conditions is not known. The literature regarding both acute and chronic cases suggests that a systematic approach to weaning involving the participation of multiple caregivers, including nurses, physicians, and respiratory, physical, and speech therapists facilitates liberation from MV. Although a gradual decrement in ventilator support would seem prudent, Scheinhorn et al have begun to identify a subpopulation of patients who can tolerate an acceleration of the weaning process. Given the known complications associated with MV, it is crucial that further research be performed to identify patients as soon as they are capable of breathing spontaneously. The literature demonstrates through multiple studies that satisfactory patient outcomes are attainable and can be achieved at LTAC facilities in a more cost-effective manner than in an ICU setting. The trend toward the concentration of patients into specialized regional weaning centers should facilitate the research process and continue to improve outcomes in this population.