This article presents a comprehensive set of goals and strategies to move nursing into its second era of knowledge development. The first era was dedicated primarily to the educational preparation of nursescholars for attainment of doctoral degrees and for the creation of research laboratories, centers, offices, and other resources and structures to support research. Era II will be recognized for more concerted work on the development of knowledge per se. Foci of a knowledge development agenda are presented, together with the new methods gaining support in nursing research to overcome the cartesian tradition of studying humans in parts rather than holistically. Process strategies to address the research agenda include postdoctorate development, collaboration, multisite studies, interorganizational pooling of resources, and international networking. The list of challenges is long and complex, but the community of scholars has a successful track record to date. The primary goal is to make some measurable progress in at least one area of knowledge development for practice in the immediate future. The positive reinforcement value of such success will carry a long way.