Determining the best method for cost analysis of end-of-life care regimens requires a systematic approach for connecting the research question being addressed with the data requirements and analyses. There are several guiding principles to direct this research, specifically in the areas of sensitivity analysis, uncertainty, generalizability, and measurement of efficiency such as cost-benefit or cost-utility. There exists a body of literature in which disease-specific or system-wide costing of health care is described, but few apply to end-of-life care. OBJECTIVE: To investigate, evaluate and present cost-analysis methods through a synthesis of recently published literature, and the implications of applying these methods to ongoing clinical studies. METHODS: Cost analyses include those acquired from articles published in professional journals in the area of cost, cost analysis and end-of-life care and applied to a set of on-going clinical studies. RESULTS: Based on a sample of nearly 30,000 'cost' studies in which few consider end-of-life care, at least eight methods for examining costs of care are defined. On one end of the spectrum is the micro-costing method in which all personnel time, supplies, cost of facilities, pharmaceuticals, lab expenses and all other patient services conducted are tracked and costed using a variety of codes. On the other end is the attributable costing method that uses aggregate and average costs for inpatient and outpatient care as well as for procedures and drugs associated with the corresponding diagnosis and treatment. Only newly initiated studies can feasibly employ micro costing. On-going studies require abstracting from other methods. CONCLUSIONS: In light of the national concern over costs associated with end-of-life care, efforts are needed to amalgamate guidelines and methodologies in this area in order to provide a useful and accessible resource to conduct meaningful cost-analysis research.