This article describes initiatives one institution developed to improve systems for detecting and preventing adverse medication events. Our discussion focuses on issues regarding the frequency and incidence of medication errors, the trials of traditional versus anonymous incident reporting, and the efforts to improve systems rather than placing blame and punishment on individuals. Initiatives such as improved documentation of pediatric patient weights and hepatic and renal function, increase of direct physician order entry into our Medical Information System (MIS), elimination of nonemergent verbal orders, and new and improved MIS ordering matrices (incorporating medical protocols and pathways) have led to more rational and efficient practices. Improved error prevention and critical incident review have identified on-going opportunities for improvement. Although the direct impact on patient outcomes is not yet measurable, numerous positive results have allowed for improved clinical decision making, streamlining of processes, increased regulatory compliance, and a positive culture change.