It was established in 1924 and is published by the American Society for Clinical Investigation.

Articles focus on the mechanisms of disease, with an emphasis on basic research, early-stage clinical studies in humans, and new research tools and techniques.

The journal also publishes reviews in edited series or as stand-alone articles, commentaries on research, editorials, and feature items.

The editor-in-chief is Elizabeth M. McNally (Northwestern University).

[6] The following persons are or have been editor-in-chief of the journal: as of October 2017[update], the following articles have received the most citations according to Scopus: