The primary goal of the present study is to provide a broad view of best practices for evaluating bioavailability models for metals for use in the protection of aquatic life. We describe the state of the science regarding 1) the evaluation and selection of ecotoxicity data, 2) the selection of bioavailability models for use in normalization, and 3) subsequent application of bioavailability models. Although many examples of normalization steps exist worldwide, a scheme is proposed to evaluate and select a model that takes account of its representativeness (water chemistry and taxonomic coverage of the ecotoxicity data set) and validation performance. Important considerations for a suitable model are the quantity of inputs needed, accuracy, and ease of use, all of which are needed to set protective values for aquatic life and to use these values to evaluate potential risks to organisms in receiving waters. Although the end results of different model application approaches may be broadly similar, the differences in these application frameworks ultimately come down to a series of trade-offs between who needs to collect the data and use the bioavailability model, the different requirements of spatial scales involved (e.g., regional vs site-specific values), and model predictiveness and protectiveness. Ultimately, understanding the limits and consequences of these trade-offs allows for selection of the most appropriate model and application framework to best provide the intended levels of aquatic life protection. Environ Toxicol Chem 2019;39:118-130. © 2019 SETAC.