This handbook “…contains a descriptive list of the stocks, confederacies, tribes, tribal divisions and settlements north of Mexico, accompanied with the various names by which these have been known, together with biographies of Indians of note, sketches of their history, archaeology, manners, arts, customs, and institutions, and the aboriginal words incorporated into the English language.”

The Handbook was the result of years of work by numerous staff members of the Federal Bureau of Ethnology, with assistance from the Office of Indian Affairs and of various other specialists. It is organized like an encyclopedia, with many short dictionary-like entries of Indian words, and some long essays on topics such as Mythology. An extensive bibliography can be found at the back of Vol. 2, and just before it is a long list of Indian words with alternate spellings.