His first paper, Molecular Engineering: An Approach to the Development of General Capabilities for Molecular Manipulation, was published in September 1981. It dealt with his vision of the benefits to be derived from nanotechnology as well as its possible downsides. The scientific community ignored him, but the Smithsonian magazine asked him to write a simplified version in 1982.

Emerging technologies and their consequences for the future became the focus of Drexler's research. He initiated studies in the field of molecular nanotechnology, a future technology based on molecular machines able to build objects to complex atomic specifications. Drexler did not coin the term nanotechnology, which means precision machining with tolerances of a micrometer or less. Nano comes from the Greek word for dwarf. Japanese researcher Norio Taniguchi put the definition together, but Drexler popularized it through his books. In the future, we can anticipate molecular manufacturing systems able to construct computers smaller than living cells, devices able to repair cells, and diamond-based structural materials. On the downside, germs could be programmed to kill people.

Drexler's first book Engines of Creation: The Coming Era of Nanotechnology, published in 1986, discussed some of these ideas and their consequences. He envisioned life-prolonging molecular machines that examine and repair cells in the human body. According to Drexler, the first nanomachines will be created for selective destruction. Cancers, infectious diseases, abnormal growths and deposits on arterial walls will be recognized by the nanomachine and destroyed. Diseases such as herpes will be cured when a repair device can be used to destroy the virus's genes. He also described solar-powered nanofactories that will remove greenhouse gases, like carbon dioxide, from the air and replace them with oxygen. These same nanofactories will be able to put carbon atoms back into coal and oil reservoirs. The book is divided into three parts. The first deals with engines of construction, principles of change, and predictions. The second part profiles the possible— engines of abundance, thinking machines, the world beyond earth, engines of healing, long life, the future, and limits to growth. The last third of the book deals with engines of destruction and strategies for survival.

In the spring of 1988, Drexler taught the first formal course in nanotechnology at Stanford University, where he was a visiting scholar from 1986 until 1991. He also founded the MIT Nanotechnology Study Group to discuss ways to cope with the unanticipated opportunities and dangers that may arise in this new field.

Drexler founded the Foresight Institute with his wife, Christine Thompson, in 1986. This organization has approximately 1,000 members. Drexler headed two conferences on nanotechnology in 1989 and 1991, and co-chaired a third in 1993. The purpose of the Institute, according to Drexler, is "… to help society prepare for new and future technologies, such as nanotechnology, artificial intelligence, and large-scale space development, by promoting an understanding of these technologies and their consequences, formulating sound policies for gaining their benefits while avoiding their dangers, informing the public and decision makers, developing an organizational base for implementing these policies, and ensuring their implementation." The Foresight Institute publishes a quarterly newsletter, the Foresight Update to keep the public informed about technical and non-technical developments in nanotechnology. The Institute for Molecular Manufacturing (IMM) is another non-profit research organization founded in 1991 to promote research in nanotechnology and molecular manufacturing. The goal of this organization is to develop nanotechnology faster. Drexler, who is a research fellow at the institute, designed a simple pump, a fine motion controller for molecular assembly, and a molecular differential gear. The last member of the Foresight family is the Center for Constitutional Issues in Technology (CCIT), a non-profit California corporation created to pursue public policy issues arising from the emergence of new technologies. In 1992, Drexler testified at a Senate hearing for the Subcommittee on Science, Technology, and Space, on the topic of molecular manufacturing.

Drexler's second book, Unbounding the Future: The Nanotechnology Revolution, was written with his wife Chris Peterson and writer Gayle Pergamit, and published in 1991. It described molecular assemblers, which are robotic arms with clamps and swivels that are small enough to pick up and reposition atoms. These assemblers would be capable of manipulating atomic and molecular ingredients used for large-scale manufacturing on Earth or in space. This type of machinery has not yet been built. Many scientists do not believe that it will ever be built.

Nanosystems: Molecular Machinery, Manufacturing, and Computation, Drexler's third book, was published in 1992. This highly technical condensation of fifteen years of research in the field of nanotechnology won the Outstanding Computer Science Book Award given by the Association of American Publishers in 1992. It is divided into three parts: the fundamental physical processes, long-term technologies (including gears and bearings, more complex machines, and molecular manufacturing systems), and practical applications from current technologies to more advanced molecular manufacturing.

While some scientists are skeptical of Drexler's view of the future, he believes that it is inevitable. In fact he predicted that nanotechnology will probably be a reality within 30 years and will make developing a room-temperature superconductor look trivial by comparison. In addition to his books and technical papers, Drexler lectures around the world. Attendance at his conventions and seminars continues to grow. Many mainstream scientists are now presenting papers at these seminars. This increased interest indicates that people are beginning to think more about the future and the form it will take.