Use of systematic reviews (SRs) as a tool to facilitate evidence-based toxicology (EBT) assessments is increasing, though the field has yet to develop an appreciation of the rigor required to appropriately utilize this tool. Toxicologists should recognize the weight of the term, understanding that a systematic review involves far more than conducting elements of a review systematically. Key aspects that appear to be currently underappreciated include development and publication of a protocol, the level of documentation involved in the conduct of a SR, and the overall level of effort required to maintain standards of SR. As many regulatory agencies and health organizations integrate systematic review into their procedures, it is clear that there is a need to develop best-science practices in EBT, as the methods developed for evidence-based medicine (EBM) do not always provide the best platform for evaluation of toxicological data. Such efforts are particularly needed for evidence integration, methods which allow for integration of multiple types of data, as well as application of the SR in both qualitative and quantitative hazard or risk assessments. Nonetheless, use of systematic review is advancing the field of toxicology, providing objectivity and transparency in evidence-based assessments.