Arrowsmith is often described as the first "scientific" novel. The books explores medical and scientific themes in a fictional way and it is difficult to think of an earlier book that does this. Although he was not a doctor, Sinclair Lewis's father was and he was greatly helped in the preparation of the manuscript by the science writer Paul de Kruif. It was de Kruif who brings a reality to the book that is almost biographical.

This reality means that the books heralds the real impact of advances in drugs, public health, and immunology that were about to change the world. It also satirises those medical and scientific practitioners whose pursuit of fame and fortune, at the expense of truth, remains just as pertinent today.

The book was first published in 1925 and was a popular and commercial success. It was awarded a Pulitzer Prize in 1926 which was refused by Sinclair Lewis. He was later to win the Nobel Prize for Literature—which he accepted.