De Kretser is an infertility and andrology expert, and a long-serving academic. He began working at Monash University in 1965, in the university's department of anatomy, and has also worked as foundation director of the Monash Institute of Reproduction and Development (recently renamed the Monash Institute of Medical Research) and as Associate Dean of the Faculty of Medicine, Nursing and Health Sciences (the Biotechnology Department). He was a senior Fellow of endocrinology at the University of Washington in Seattle from 1969 to 1971.
De Kretser has been married to Jan for over 40 years, and has four sons: Steve, Mark, Ross and Hugh. Ross and Steve are Chemical Engineers, Mark is a General Practitioner, and Hugh is a Human Rights lawyer.