In 1978, the BBC tasked producer Bill Sellars with the creation of a television series from James Herriot's first two novels, If Only They Could Talk and It Shouldn't Happen to a Vet, using the title of the 1975 film adaptation All Creatures Great and Small.

The leading role was taken by a relatively unknown actor Christopher Timothy, after Simon Ward, John Alderton and Richard Beckinsale all turned it down. Siegfried Farnon was played by the well-known Robert Hardy.

Tristan was played by Peter Davison (who became a household name as a result, and went on to take many other starring roles, notably as the fifth incarnation of the Doctor in Doctor Who and as Margery Allingham's detective Albert Campion in two series of Campion).

Helen was played by Carol Drinkwater in the first three series and two specials and she had a real life romance with Christopher Timothy. Mary Hignett played the housekeeper Mrs. Hall, and Margaretta Scott appeared as the recurring aristocratic dog-owner Mrs Pumphrey.

With the amount of time available to it, the series quickly became much more of an ensemble show, developing all the characters considerably. In particular, the role of Tristan was significantly increased, partly because Christopher Timothy suffered an automobile accident part-way through the first series and so was restricted to studio shooting (in at least one episode, he can be seen having visible difficulty walking about the surgery), requiring that scenes involving location filming be rewritten and given to Davison.

The programme ran for three series, but broke off in 1980 at the stage where the characters were drawn into the Second World War. Two specials were subsequently made in 1983 and 1985, and then in 1988 the programme was revived, and ran for four more series carrying on the story after the war.

In the revived series, Lynda Bellingham took over the role of Helen, and Judy Wilson played a new housekeeper, Mrs. Greenlaw, as Mary Hignett had died shortly after the end of the third series.

The Darrowby practice added a young vet with a liking for badgers in the form of John McGlynn playing Calum Buchanan (based upon Herriot's real-life assistant Brian Nettleton), a former classmate of Tristan's.

The Herriot children, who had been introduced in the two specials, now became recurring characters, with Jimmy played by Oliver Wilson and Rosie by Rebecca Smith.