As background for a National Institutes of Health State of the Science Conference on End-of-Life-Care, we performed a systematic review of end-of-life care and outcomes. The systematic review was intended to evaluate the evidence in the field from the perspective of concerns important to patients, caregivers, and the health care system. This article relates the challenges in performing a systematic review of end-of-life care and outcomes, and describes the methods that we used to define the scope, search the literature, develop exclusion and inclusion criteria, incorporate various types of articles, and synthesize the results. Major challenges to conducting a review included the need to define "end of life," clarify a conceptual framework of outcomes including definitions of terms and the relationships among terms, and determine specific goals for the review. The review identified 24,423 total citations, of which 911 comprised the final set used for the evidence report. This very large, diverse body of literature reflects the tremendous growth of the field of end-of-life care over the last decade.