ISB was co-founded in 2000 in Seattle, Washington by Dr. Leroy Hood, an immunologist and technologist; Dr. Alan Aderem, an immunologist and Dr. Ruedi Aebersold, a protein chemist. It has since grown to more than 300 staff members, including 13 faculty members and laboratory groups.

The Institute emerged as a result of the new research model called systems biology a revolutionary approach to analyzing biological complexity and understanding how biological systems function. The Institute has brought together a multidisciplinary group of scholars and scientists, from biologists, mathematicians and engineers, to computer scientists and physicists, in an interactive and collaborative environment. There are very few places with such a diverse representation of backgrounds and experience under one roof.