The ultimate goals of nursing research are knowledge generation and improvement in nursing practice. Designing studies that provide the evidence needed for practice change and that have clear implications for immediate application to current practice environments is particularly challenging. Research programs that consist of sequential studies, each building on and expanding on the results of the previous work, offer the greatest promise for generating understanding of the human phenomenon relevant to nursing practice. The authors review their experience with a series of studies of inpatient and postdischarge needs and interventions associated with chronic critical illness to illustrate the benefits of developing a longitudinal research program as well as the importance of strategies that will foster application of results. Recommendations for developing such a program are discussed.