This chapter outlines the advantages of the zebrafish for mitochondrial toxicology studies and the tools, models, and methods that have been developed to study mitochondrial toxicology in zebrafish, as well as what has been learned from these studies. The use of zebrafish as a model for genetic studies stems from the work by Dr George Streisinger in the late 1960s to early 1970s. Zebrafish require an aquatic environment, and thus do not need lungs, but instead require a swim bladder and gills. Researchers can also challenge the zebrafish to exercising and recovery using swim tunnels. These tunnels allow for the monitoring of not only swimming behavior but also physiological measurements, such as oxygen consumption. Zebrafish are an excellent model system for mitochondrial biology and diseases. Because zebrafish embryos and early-stage larvae are small and can fit easily into up to 384-well plates, many mitochondrial assays can be translated from cell culture.