Engines of Creation is unique for its style and substance. It makes oblique literary references; the section on hypertext references the Samuel Taylor Coleridge poem "Xanadu" while discussing the concepts first developed by the Project Xanadu while never mentioning Coleridge by name. A section on life extension is entitled "Worlds Enough And Time" but never names the Andrew Marvell poem from which the phrase is taken ("To His Coy Mistress").
The substance of Engines of Creation is unique as well. Various science fiction writers have used the concept of tiny machines. Physicist Richard Feynman discussed it in his speech "There's Plenty of Room at the Bottom". But only Drexler came up with the idea of self-replicating robots at the molecular scale.
With the publication of Engines of Creation Drexler founded the first group for preparing society for molecular nanotechnology. Drexler took the unusual step of securing permission from the publisher to include the post office box for the Foresight Institute, a group that did not yet exist.
Engines of Creation is often abbreviated "EOC" in online discussions.