Toxic substances have been suspected of being one of the causes of Great Lakes lake trout reproductive failure. Because toxic substances are present in the Great Lakes basin, managers should be aware of the role of contaminants in preventing lake trout rehabilitation. This paper summarizes studies which have sought to establish a relation between toxic substances and lake trout mortality or morbidity, and offers recommendations for future research and management. The review suggests that exposure to toxic substances has the possibility of affecting the species' rehabilitation. A variety of toxic substances, specifically organochlorine compounds, concentrated in lake trout eggs, fry, and the environment, have affected the hatching success of lake trout in the laboratory, but the strength of the relation between toxic substances and lake trout mortality and morbidity in the field remains unclear. In order to clarify this relation, more information is needed on lake trout physiology, biochemistry, behavior, and genetics. An interdisciplinary workshop should be convened to evaluate existing evidence by epidemiological methods, to set priorities for further research, and to develop management strategies.