Historically, negative clinical and economic outcomes have been associated with patients who need long-term mechanical ventilation. Institutions and clinicians charged with the care of these patients are understandably interested in exploring clinical strategies that assure positive outcomes. This article describes the evidence base for clinical pathways, weaning teams, protocols, and care-managed approaches. In addition, the article describes how different elements of system initiatives designed for a university teaching hospital and a community hospital were implemented and evaluated. The systematic approaches encourage multidisciplinary input and decrease variation, thus improving both quality and cost.