This paper reviews the career and legacy of William (Bill) Goffman, who served as a researcher, Professor, Dean and Emeritus at Case Western Reserve University, Cleveland, Ohio, from 1959 to 2000. Goffman pioneered mathematical information science broadly and in several key areas. First, he applied disease epidemiology concepts to model accurately the spread of knowledge and the formation of knowledge systems and their ecologies, including the dynamics of scientific discovery. Second, he proposed significant improvements in information retrieval through the deployment of multi-valued logic, appropriate file ordering, effective and efficient retrieval measures, and simplified retrieval approaches, including early work in citation-based searching. Third, Goffman applied Bradford-like distributions to model effective core research literature collection development and usage. Fourth, he developed original epidemiology models, and was an early contributor in biomedical informatics. His mat...