The journal was established in 1909 by Thomas Lewis and James Mackenzie under the title Heart: A Journal for the Study of the Circulation.^[1][2] Lewis was the first editor-in-chief.^[3] In 1933, Lewis renamed the journal Clinical Science (ISSN 0009-9287; 1933–1973), his interests having broadened.^[1] It was briefly retitled Clinical Science and Molecular Medicine (ISSN 0301-0538; 1973–1978), becoming Clinical Science again in 1979.^[4][5][6]

The journal was published by the Medical Research Society (founded by Lewis in 1930)^[1] from 1945 until 1961, and then jointly by the Medical Research Society and the Biochemical Society until 2003, when the latter became the sole publisher.^[7][8] It was formerly published by Blackwell Science.^[4]