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OBJECTIVE: To highlight the importance of insulin-related medical errors in causing poor outcomes in a hospital setting and to propose a systems approach for improvement. RESULTS: Evidence reported in the medical literature has identified insulin therapy errors as a large and clinically important problem. Insulin has been labeled as one of the top five "high-risk medications" in the inpatient setting. Although insulin therapy can be lifesaving in the hospital setting, it can be life-threatening if used inappropriately. Widespread major systemic problems, such as heavy patient loads for physicians and nurses, absence of backup checks in critical areas, defective communication and coordination, illegible handwriting, and unawareness of the importance of blood glucose control, create obstacles to appropriate and safe care of patients receiving insulin in the hospital. With thorough analysis of the setting, additional training, collective establishment of goals focused on patient safety, insertion of backup checks in areas susceptible to errors, encouragement of sharing of key clinical information, and, where possible, implementation of electronic medical records, systemic and knowledge-based problems will be minimized and outcomes will improve in insulin-treated hospitalized patients. CONCLUSION: Analysis and redesign of systems to develop a "culture of safety" will ultimately reduce insulin-related medical errors, provide a safe inpatient environment, and yield better outcomes.