Workshops sponsored by the Institute of Medicine (IOM) and the World Health Organization suggested that incorporating systematic (evidence) reviews into the process of updating nutrient reference values would provide a comprehensive and distilled evidence document to decision makers and enhance the transparency of the decision-making process the IOM used in recommending the Dietary Reference Intake values (DRIs) for US and Canadian populations. At the request of the US and Canadian government sponsors of the ongoing review of the 1997 vitamin D and calcium DRI values, the Tufts Evidence-based Practice Center performed a systematic review for the current DRI Committee to use early in its deliberations. We described the approach used to include systematic review into the IOM process for updating nutrient reference values and highlighted major challenges encountered along with the solutions used. The challenges stemmed from the need to review and synthesize a large number of primary studies covering a broad range of outcomes. We resolved these challenges by 1) working with a technical expert panel to prioritize and select outcomes of interest, 2) developing methods to use existing systematic reviews and documenting the limitations by doing so, 3) translating results from studies not designed to address issues of interest by using a transparent process, and 4) establishing tailored quality-assessment tools to assist in decision making. The experiences described in this article can serve as a basis for future improvements in systematic reviews of nutrients and to better integrate systematic review into development of future nutrient reference values.