The Krebs Institute for Biomolecular Research was set up by the University of Sheffield in 1988 and formally inaugurated in April 1989 at a ceremony attended by Lady Margaret Krebs and other members of the family after whose most eminent member, Professor Sir Hans Adolf Krebs, Nobel Laureate, the Institute was named. Professor Dorothy Hodgkin, OM, FRS and Nobel Laureate gave an Inauguration Lecture in Firth Hall as guest speaker on the occasion.

The Institute had as its first director Dr Paul C. Engel, lecturer in the Department of Biochemistry, Division of Molecular Biology and Biotechnology. Its character is defined in the staff handbook as `an interdisciplinary research consortium, comprising staff from several departments with a common interest in understanding the structural basis of the activity of biological molecules´. Early documentation specifies that membership was open to those `involved in collaborative research on biological processes at the molecular level, from departments in the Faculty of Pure Science.

In August 1994 Dr Engel moved to University College, Dublin, as Professor of Biochemistry and Professor David W. Rice became the Institute´s new director.