The importance of active and engaged hospital leadership in improving safety was highlighted by a Joint Commission Sentinel Event Alert, which challenged hospital executives and boards to establish a culture of safety and systematically analyze and address safety issues. This article details a checklist that hospital leadership can use to organize efforts to eliminate central line–associated bloodstream infections. This AHRQ-funded effort is centered around principles of the comprehensive unit-based safety program and includes specific interventions successfully used in the Keystone ICU project. Prior studies have shown that hospital boards are sometimes surprisingly disengaged from safety efforts, and this article provides a blueprint for executives to direct focused and institution-wide safety projects.