Health reform worldwide is required due to the largely aging population, increase in chronic diseases, and rising costs. To meet these needs, nurses are being encouraged to practice to the full extent of their skills and take significant leadership roles in health policy, planning, and provision. This can involve entrepreneurial or intrapreneurial roles. Although nurses form the largest group of health professionals, they are frequently restricted in their scope of practice. Nurses can help to improve health services in a cost effective way, but to do so, they must be seen as equal partners in health service provision. This article provides a global perspective on evolving nursing roles for innovation in health care. A historical overview of entrepreneurship and intrapreneurship is offered. Included also is discussion of a social entrepreneurship approach for nursing, settings for nurse entre/intrapreneurship, and implications for research and practice.