Stephen Safe was a Research Officer at the National Research Council of Canada from 1968 to 1973. He then became an Associate Full Professor in the Department of Chemistry at the University of Guelph from 1973 to 1981. He came to the Department of Veterinary Physiology and Pharmacology at Texas A&M University in 1981 and received the title of Distinguished Professor in 1984. Research in his laboratory focuses on developing and discovering compounds for mechanism-based drug development that target both cancer and non-cancer endpoints.