The field of environmental toxicology developed as a result of growing concerns about anthropogenic influences on the environment and how to ameliorate ecological impact. Many governmental bodies are beginning to emphasize prevention rather than mitigation when addressing novel products, leading to more of a focus on identifying potential toxicity prior to release. With the exponential advances in their development and sale, novel metamaterials and biotechnology are set to dramatically outpace the capabilities of current testing strategies. To address the need for a fast, cost‐effective means of testing chemicals, high‐throughput screening (HTS) is currently being used in toxicology and being adapted to ecotoxicology in projects such as ToxCast and Tox21. Despite the growth of research using HTS platforms, its role in ecotoxicology is still uncertain, particularly in how it should be applied in regulation. The aim of the present review is to discuss common test strategies used in designing HTS platforms, the current potential applications for ecotoxicological research, its role in regulatory policies, and its ability to address growing concerns such as engineered nanomaterials. Environ Toxicol Chem 2017;36:1704–1714. © 2017 SETAC