Orla Smith received a B.Sc in Zoology in 1982 from King's College, University of London (London, UK), and a Ph.D. in Biochemistry in 1987 from the Royal Free Hospital School of Medicine, University of London (London, UK). From 1988 to 1992 she was a Hunkel-MACC postdoctoral fellow at the Medical College of Wisconsin, Milwaukee, Wisconsin, USA, and continued her postdoctoral work until 1995 at the Johns Hopkins Oncology Center, Baltimore, Maryland, USA.

In 1996 she left the bench to become the News and Views Editor at Nature Medicine. In 1999, she was appointed Senior Editor at Science magazine.