Martin Arrowsmith enters medical school with the dream of becoming a great scientist. Once he gets there, he's sad to discover that other med students are only interested in making lots of money and gaining fame. Martin's one great ally in his quest for capital-T scientific Truth is a crabby old professor, Max Gottlieb. But Martin has a lot of trouble living up to Gottlieb's expectations.
Meanwhile, Martin starts dating two women at once and becomes engaged to both of them. Don't hate the player; hate the game? Maybe? He eventually chooses one of them—named Leora—and moves with her to her hometown after he finishes medical school.
He eventually gets run out of town for being too honest with people (his version of events) or being too cold and pretentious (the town's version of events). After taking another job in another city, he again gets pushed out of his job for not playing the political games he needs to.
With no job and no decent prospects, Martin gets a letter from Max Gottlieb offering him a job at the McGurk Institute, a place where scientists can pursue their research interests without having to play politics or please their community. It sounds like a dream come true, and in many ways it is.
During his time at McGurk, Martin stumbles upon a possible cure for pneumonia. But instead of publishing the news right away, he spends more than a year trying to test his findings. By the time he's ready to publish, someone in France has already beaten him to it. His scientific morals have cost his institution a lot of money and fame, and his bosses are none too pleased.
After the whole pneumonia-cure fiasco, Martin decides to travel to a plague-infected Caribbean island to test a new vaccine. It's going to be difficult because the only way he can truly test the vaccine's effectiveness is to leave half of the infected people untreated and to let them die. Moral quandary, much?
While he's on the island, though, his wife Leora dies and Martin decides that he's finished with using the islanders as guinea pigs. He gives everyone the vaccine and returns home a widower.
After recovering from the loss of Leora, Martin marries a beautiful and rich young woman who bustles him off to a bunch of swanky parties. He feels like a total sellout and eventually leaves his wife to go work on his experiments in a shack in Vermont. When his wife comes after him, he decides to leave her forever and to keep pursuing scientific Truth until he dies.