Whilst under his tutorage, Shepherd was asked to visit a patient in her own home in Cowley in order to learn about the socio-medical significance of cardiac invalidism.

In 1954 he obtained his Doctorate in Medicine from Oxford University, his thesis being a study of the pattern of major psychoses in the county of Buckinghamshire during two periods, 1931–33 and 1945–47.

He established the General Practice Research Unit at the Institute of Psychiatry in the late 1950s and continued to direct its activities until his retirement in 1988.

[2] Shepherd was heavily influenced during his early years at The Maudsley by Aubrey Lewis, who taught that the precise and well-organised collection of social data should become a new activity for the psychiatrist rather than limiting himself to the clinical study of the individual patient.

With the exception of one year's attachment to the School of Public Health at Johns Hopkins University, Baltimore, in 1955–56,[3] Shepherd remained at The Maudsley for the entire duration of his professional career.

[1] Shepherd's research and influence led to a closer scrutiny of the needs of the numerous patients encountered in general practice with psychological disorders.

[5][6] Shepherd's work Psychiatric Illness in General Practice (1966) greatly changed this area of mental health research.

[2] Shepherd's noted clinical study on the symptom of morbid jealousy early in his career led him to the conclusion that a medical opinion is of most value when the inter-personal and social aspects of a case are as closely understood as the narrower issue of diagnosis.

His detachment was described as "Olympian" and was captured by a former patient in the lines of her book thus: "a tall dark pale man, with a chillingly superior glance and quellingly English voice made another appointment to see me.

He went on to instigate the move towards obtaining international agreement for the definition of schizophrenia in the communicable form[9] He also wrote extensively on the general psychopathology of Karl Jaspers[10] illuminating his belief that the main appeal of Jaspers' book as its breadth in extending the field of general psychopathology from the natural sciences, via phenomenology, to existentialist philosophy.

Most notable are those centred on the achievements of people he admired including John Ryle, Aubrey Lewis and Jean Starobinski.

[11] Kenneth Rawnsley suggested that he identified in his mentor the very qualities that he aspired to himself: intellectual integrity, scholarship, a vast range of knowledge and a cultivated capacity for juridical thought.

He aimed to concentrate on original high-quality work across the wide spectrum of both psychiatry and its allied disciplines and contributed extensively himself investing much time and care towards its success.

[2] He married Margaret Rock in 1947, a school teacher and together they had four children, two daughters, Catherine and Lucy, and two sons, Simon and Daniel, whom they raised in a large house on Alleyn Park Road in West Dulwich, south London, a relatively short distance from Maudsley Hospital.