Environmental restoration, regulatory protections, and competing interests for water are changing the balance of selenium (Se) discharges to the San Francisco Bay–Delta Estuary (Bay–Delta). The model for Se described here as part of the Delta Regional Ecosystem Restoration Implementation Plan (DRERIP) draws both from the current state of knowledge of the Bay–Delta and of environmental Se science. It is an ecosystem-scale methodology that is a conceptual and quantitative tool to (1) evaluate implications of Se contamination; (2) better understand protection for fish and aquatic-dependent wildlife; and (3) help evaluate future restoration actions. The model builds from five basic principles that determine ecological risks from Se in aquatic environments: (1) dissolved Se transformation to particulate material Se, which is partly driven by the chemical species of dissolved Se, sets dynamics at the base of the food web; (2) diet drives bioavailability of Se to animals; (3) bioaccumulation differs widely among invertebrates, but not necessarily among fish; (4) ecological risks differ among food webs and predator species; and (5) risk for each predator is driven by a combination of exposures via their specific food web and the species’ inherent sensitivity to Se toxicity. Spatially and temporally matched data sets across media (i.e., water, suspended particulate material, prey, and predator) are needed for initiating modeling and for providing ecologically consistent predictions. The methodology, applied site-specifically to the Bay–Delta, includes use of (1) salinity-specific partitioning factors based on empirical estuary data to quantify the effects of dissolved speciation and phase transformation; (2) species-specific dietary biodynamics to quantify foodweb bioaccumulation; and (3) habitat use and life-cycle data for Bay–Delta predator species to illustrate exposure. Model outcomes show that the north Bay–Delta functions as an efficient biomagnifier of Se in benthic food webs, with the greatest risks to predaceous benthivores occurring under low flow conditions. Improving the characterization of ecological risks from Se in the Bay–Delta will require modernization of the Se database and continuing integration of biogeochemical, ecological, and hydrological dynamics into the model.