Infections are the second leading cause of death for patients with ESKD. Despite multiple efforts, nephrologists have been unable to prevent infections in dialysis facilities. The American Society of Nephrology and the Centers for Disease Control and Prevention have partnered to create Nephrologists Transforming Dialysis Safety to promote nephrologist leadership and engagement in efforts to "Target Zero" preventable dialysis infections. Because traditional approaches to infection control and prevention in dialysis facilities have had limited success, Nephrologists Transforming Dialysis Safety is reconceptualizing the problem in the context of the complexity of health care systems and organizational behavior. By identifying different parts of a problem and attempting to understand how these parts interact and produce a result, systems thinking has effectively tackled difficult problems in dynamic settings. The dialysis facility is composed of different physical and human elements that are interconnected and affect not only behavior but also, the existence of a culture of safety that promotes infection prevention. Because dialysis infections result from a complex system of interactions between caregivers, patients, dialysis organizations, and the environment, attempts to address infections by focusing on one element in isolation often fail. Creating a sense of urgency and commitment to eradicating dialysis infections requires leadership and motivational skills. These skills are not taught in the standard nephrology or medical director curriculum. Effective leadership by medical directors and engagement in infection prevention by nephrologists are required to create a culture of safety. It is imperative that nephrologists commit to leadership training and embrace their potential as change agents to prevent infections in dialysis facilities. This paper explores the systemic factors contributing to the ongoing dialysis infection crisis in the United States and the role of nephrologists in instilling a culture of safety in which infections can be anticipated and prevented.