“Weight of evidence” (WOE) is a common term in the published scientific and policy-making literature, most often seen in the context of risk assessment (RA). Its definition, however, is unclear. A systematic review of the scientific literature was undertaken to characterize the concept. For the years 1994 through 2004, PubMed was searched for publications in which “weight of evidence” appeared in the abstract and/or title. Of the 276 papers that met these criteria, 92 were selected for review: 71 papers published in 2003 and 2004 (WOE appeared in abstract/title) and 21 from 1994 through 2002 (WOE appeared in title). WOE has three characteristic uses in this literature: (1) metaphorical, where WOE refers to a collection of studies or to an unspecified methodological approach; (2) methodological, where WOE points to established interpretative methodologies (e.g., systematic narrative review, meta-analysis, causal criteria, and/or quality criteria for toxicological studies) or where WOE means that “all” rather than some subset of the evidence is examined, or rarely, where WOE points to methods using quantitative weights for evidence; and (3) theoretical, where WOE serves as a label for a conceptual framework. Several problems are identified: the frequent lack of definition of the term “weight of evidence,” multiple uses of the term and a lack of consensus about its meaning, and the many different kinds of weights, both qualitative and quantitative, which can be used in RA. A practical recommendation emerges: the WOE concept and its associated methods should be fully described when used. A research agenda should examine the advantages of quantitative versus qualitative weighting schemes, how best to improve existing methods, and how best to combine those methods (e.g., epidemiology's causal criteria with toxicology's quality criteria).