Drexler participated in NASA summer studies on space colonies in 1975 and 1976. He fabricated metal films a few tens of nanometers thick on a wax support to demonstrate the potentials of high performance solar sails. He was active in space politics, helping the L5 Society defeat the Moon Treaty in 1980.
During the late 1970s, he began to develop ideas about molecular nanotechnology (MNT). In 1979, Drexler encountered Richard Feynman's provocative 1959 talk There's Plenty of Room at the Bottom. The term nanotechnology was coined by the Tokyo Science University Professor Norio Taniguchi in 1974 to describe the precision manufacture of materials with nanometer tolerances, and was unknowingly appropriated by Drexler in his 1986 book Engines of Creation: The Coming Era of Nanotechnology to describe what later became known as molecular nanotechnology (MNT). In that book, he proposed the idea of a nanoscale "assembler" which would be able to build a copy of itself and of other items of arbitrary complexity. He also first published the term "grey goo" to describe what might happen if a hypothetical self-replicating molecular nanotechnology went out of control.
Drexler holds three degrees from MIT He received his S.B. in Interdisciplinary Sciences in 1977 and his S.M. in 1979 in Astro/Aerospace Engineering with a Master's thesis titled "Design of a High Performance Solar Sail System,." In 1991 he earned a Ph.D. under the auspices of the MIT Media Lab (formally, the Media Arts and Sciences Section, School of Architecture and Planning). His Ph.D. work was the first doctoral degree on the topic of molecular nanotechnology and (after some editing) his thesis, "Molecular Machinery and Manufacturing with Applications to Computation," was published as "Nanosystems: Molecular Machinery, Manufacturing and Computation" (1992), which received the Association of American Publishers award for Best Computer Science Book of 1992.
Drexler and Christine Peterson, at that time husband and wife, founded the Foresight Institute in 1986 with the mission of "Preparing for nanotechnology.” Drexler and Peterson ended their 21-year marriage in 2002. Drexler is no longer a member of the Foresight Institute.
In August 2005 Drexler joined Nanorex, a molecular engineering software company based in Bloomfield Hills, Michigan, to serve as the company's Chief Technical Advisor. Nanorex's nanoENGINEER-1 software was reportedly able to simulate a hypothetical differential gear design in "a snap". According to Nanorex's web site, an open source molecular design program is currently slated for release in Fall 2007.
In 2006, Drexler married Rosa Wang, a former investment banker who works with Ashoka: Innovators for the Public on improving the social capital markets.
One of the barriers to achieving molecular nanotechnology is the lack of an efficient way to create machines on a molecular/atomic scale. One of Drexler's early ideas was an "assembler," a nanomachine that would comprise an arm and a computer that could be programmed to build more nanomachines. If an assembler could be built, it might then build a copy of itself, and thus potentially be useful for efficient mass production of nanomachines. But the lack of a way to first build an assembler remains the sine qua non obstacle to achieving this vision.
A second difficulty in reaching molecular nanotechnology is design. Hand design of a gear or bearing at the level of atoms is a gruelling task. While Drexler, Merkle and others have created a few designs of simple parts, no comprehensive design effort for anything approaching the complexity of a Model T Ford has been attempted.
A third difficulty in achieving molecular technology is separating successful trials from failures, and elucidating the failure mechanisms of the failures. Unlike Darwinian evolution, which proceeds by random variations in ensembles of organisms combined with deterministic reproduction/extinction as a selection process to achieve great complexity after billions of years (a set of mechanisms that Richard Dawkins has referred to as a "blind watchmaker"), deliberate design and building of nanoscale mechanisms requires a means other than reproduction/extinction to winnow successes from failures. Such means are difficult to provide (and presently non-existent) for anything other than small assemblages of atoms viewable by an AFM or STM.
Thus, even in the latest report A Matter of Size: Triennial Review of the National Nanotechnology Initiative put out by the National Academies Press in December 2006, (roughly twenty years after Engines of Creation was published) no clear way forward toward molecular nanotechnology is seen, as per the conclusion on page 108 of that report: "Although theoretical calculations can be made today, the eventually attainable range of chemical reaction cycles, error rates, speed of operation, and thermodynamic efficiencies of such bottom-up manufacturing systems cannot be reliably predicted at this time. Thus, the eventually attainable perfection and complexity of manufactured products, while they can be calculated in theory, cannot be predicted with confidence. Finally, the optimum research paths that might lead to systems which greatly exceed the thermodynamic efficiencies and other capabilities of biological systems cannot be reliably predicted at this time. Research funding that is based on the ability of investigators to produce experimental demonstrations that link to abstract models and guide long-term vision is most appropriate to achieve this goal."
In the science fiction novel Newton's Wake by Ken Macleod a 'drexler' is a nanotech assembler of pretty much anything that can fit in the volume of the particular machine - socks to starships.
Drexler is also mentioned in the science fiction book Decipher by Stel Pavlou, his book is mentioned as one of the starting points of the nanomachine construction, as well as giving a better understanding of the way carbon 60 was to be applied.
James Rollins references Drexler's Engines of Creation in his novel Excavation, using his theory of a molecular machine in two sections as a possible explanation for the mysterious "Substance Z" in the story.