Technical Abstract: Workshops sponsored by the Institute of Medicine (IOM) and the World Health Organization (WHO) suggested that incorporating systematic reviews into the process of updating nutrient reference values would enhance the transparency of the process. The IOM issues the Dietary Reference Intake values (DRIs) for US and Canadian populations. At the request of the US and Canadian governments, sponsors of the ongoing review of the 1997 DRIs for vitamin D and calcium, the Tufts University Evidence-based Practice Center (EPC) performed a systematic review to be made available to the current DRI Committee early in its deliberative process. This was the first time that an independent systematic review has been commissioned to coincide with an ongoing DRI process. This paper describes the approach and methodology used for the systematic review and highlights the major challenges encountered, along with their solutions. These include the need to prioritize and clearly formulate key questions, select outcomes of interest, document limitations of existing literature for establishing nutrient reference values, and establish tailored quality assessment tools to assist decision making. The experiences described in this paper can serve as basis for future advances in methodology when integrating systematic review into development of future nutrient reference values.