By the year 2020, as hospitals morph into entirely different kinds of service providers, nurses too will look altogether different. Those with the capacity to embrace disruptive innovation, along with all the unknowns that accompany it, will be successful at guiding their organizations into the future. Nurse executives must act now to build nursing cultures capable of massive and transformational change—change that will alter the way patient care is perceived, delivered, and evaluated. One hospital system is using a Think Tank approach to pilot demonstration projects that aim to maximize the role of the registered nurse and redefine expectations around patient care delivery. Early work indicates that new thinking combined with “permission to fail” from nursing leadership is essential to success. Lean Six Sigma principles and creativity tools from inside and outside of health care are being adopted with promising results. Exemplars show that by creating a sense of urgency around a big opportunity, this health care system is developing change initiatives that are literally transforming culture.