Nursing informaticists can be leaders in promoting prevention of illness and diseases in the 21st century. Developing an infrastructure for application of preventive and predicative models in healthcare delivery is paramount. This chapter stresses the need for rural regions to develop paradigmatic models for incorporating all aspect of the human ecology domain. While movement in public health nursing is contingent on improvement in public health interconnectivity, nurse informaticists need to develop a classification system for public health nursing, develop databases for evidence–based practice, and incorporate the rural culture in their work. Incorporation of genomics in daily nursing practice will soon be a reality. As consumer-driven healthcare becomes the reality, the platform for healthcare delivery will change. A change to care delivery in a variety of community sites with electronic information exchanges and personal health records will require robust work by informaticists. Remote monitoring devices in clients’ homes are another arena which will require a new set of skills for nursing interventionists.