- The town Street Urchin, who has been harassing James and other town-folk, brings his dog in with distemper. While James desperately tries to cure the dog, the boy becomes a model citizen and even takes on odd jobs to pay for the care. The TV version is hard enough to sit through with a dry eye, but the book makes it worse by suggesting that his dog was the only thing keeping the boy from a very bad end.
- A married couple are planning to split up, but stay together because their dog is dying. If you thought the experience would bring them together and convince them to give it another try, well....
- Paul Cotterell, a friendly local dog owner, (played by Nicholas Courtney) brings in his dog Theo because he's been losing weight. James discovers it has cancer, and they have to put it down. Paul remains calm, and though sad, accepting, throughout the procedure. Then, a few days later, James finds out he's committed suicide.
- The entire episode "Big Steps and Little 'uns", the third season finale (and, for a while, the series finale.) To start, we have Siegfried and James preparing to leave Yorkshire to fight in the war. They are kept out all day on various cases, so they stay up all night talking, neither willing to say goodbye, not knowing if they'll ever see each other again. Another mention goes to James saying goodbye to Helen, Mrs. Hall sending him off in tears, and Tristan, who has just been officially certified as a vet, promising to hold down the fort while James and Siegfried are away. This is also the last episode with Mrs. Hall, as Mary Hignett died of complications from hip surgery just a few months after it aired.
Tear Jerker / All Creatures Great and Small
There are many, since the series never whitewashes the fact that animals often die or have to be put down. But some are especially notable.