Conservation of native fish is a pressing issue for fisheries managers. Conservation efforts often require eliminating threats posed by nonnative fish by eradicating them with piscicides. The piscicides rotenone and antimycin are used for eradication but their application is often inefficient or ineffective. My goal was to increase the efficiency and efficacy of nonnative fish eradication using piscicides. I identified environmental conditions affecting piscicide application, researched methods to overcome these problems, and provided tools that piscicide applicators can use to make piscicide application more efficient and effective. Rotenone and antimycin were exposed to varying levels of sunlight, turbulence, and dissolved organic matter (DOM) to determine the effect these environmental conditions have on piscicides. Bioassay fish were used to determine the toxicity of the piscicides. Sunlight and turbulence affected rotenone and antimycin but DOM did not. Increasing the concentration of chemical can increase the resistance to the effects of these environmental conditions; however, the effects of these conditions are considerable in natural settings. Observations of bioassay fish in stream applications of rotenone were used to develop a statistical model to predict the persistence of the piscicide. The model can be used to predict rotenone persistence in small montane streams and to estimate where rotenone concentrations need to be fortified. I measured the mixing rate of a chemical plume in different channel morphologies and at center or edge applications. Center application had a significantly shorter mixing distance than edge application, but mixing distance was not different among meandering, straight, and riffle/pool morphologies. Application of my findings will increase the efficiency and efficacy of native fish conservation using piscicides.