Population modeling, field studies, and monitoring approaches have all been proposed for assessing the relevance of adverse effects of endocrine disrupting chemicals (EDCs) at the population level for nontarget (wild) vertebrates, but how these approaches should be used in the regulatory hazard assessment is unclear and not detailed in the relevant European Guidance Document. A literature review focused on identifying published approaches assessing the population relevance of adverse effects from EDCs was performed, and, subsequently, 47 primary research papers were evaluated. By extracting from these sources, a novel approach was developed with guiding principles for assessing adverse effects of EDCs at the population level considering (i) choice of focal species, scenarios (and models), (ii) the individual level apical endpoints to be considered, (iii) the magnitude of effect to be imposed, (iv) for what duration effects should be imposed, (v) whether individuals repairing the damage from exposure should be included, (vi) the population-level endpoints to be considered, and (vii) what threshold to set for defining an adverse effect at this level. Recommendations for modeling and field and monitoring studies are included. Case studies are also presented to demonstrate how the proposed approach might be implemented. Although some aspects (e.g., choice of focal species, model/experimental scenario, monitoring study assessment) require further consideration, this should not prevent the use of this approach in a regulatory EDC assessment context. As such, we propose that the approach be used immediately to implement population modeling and perform field studies within this regulatory context. We envisage that consistent application of these principles will encourage regulatory developments in this critical area to provide a much needed level of clarity in the EDC assessment for all stakeholders.