The book employs a narrative conceit that, under subtle inspiration, the novelist has unknowingly been dictated a channelled text from the last human species.

The book anticipates the science of genetic engineering, and is an early example of the fictional supermind: a consciousness comprising many telepathically linked individuals.

Another Stapledon novel, Star Maker (1937), could also be considered a sequel to Last and First Men (mentioning briefly man's evolution on Neptune), but is even more ambitious in scope, being a history of the entire universe.

C. S. Lewis, in his own preface to That Hideous Strength, notes: "I believe that one of the central ideas of this tale came into my head from conversations I had with a scientific colleague, some time before I met a rather similar suggestion in the works of Mr. Olaf Stapledon.

"[4] H. P. Lovecraft held the book in very high regard (though he did not say whether it influenced any of his own stories), saying in a 1936 letter to Fritz Leiber[5] "no one ought to miss reading W. Olaf Stapledon's Last and First Men...

", and in another 1936 letter to Leiber[6] "I'm glad to hear of your perusal of Last and First Men—a volume which to my mind forms the greatest of all achievements in the field that Master Ackerman would denominate "scientifiction".

But I do like the few real masterpieces in the field—certain of H. G. Wells's novels, S. Fowler Wright's The World Below, & that marvellous piece of imagination by W. Olaf Stapledon, Last & First Men."

John Maynard Smith has said "A man called Olaf Stapledon was a marvellous predictor who wrote science fiction books that I read when I was 16 and that completely blew my mind; and Arthur C. Clarke put his finger on quite a number of bright thoughts.