Advancing the science of end-of-life care requires a foundation of clear domains and variables to guide research and clinical practice. Palliative care and hospice programs have grown rapidly in recent years in response to an increasing proportion of the population living with chronic, debilitating, and life-threatening illness. Numerous studies and key publications have proposed frameworks that identify key concepts or domains of end-of-life care. A major advance in defining the essential domains of palliative care has been the release in 2004 of national guidelines published by the National Consensus Project for Quality Palliative Care (NCP). This paper reviews and compares several models that have proposed domains of end-of-life care and then applies the domains of the NCP Clinical Practice Guidelines as a framework to identify potential outcome variables for research. Having definitions and concepts shared by scientists in end-of-life care can advance the science and provide an evidence base for practice to improve quality care.