Starting in the late 1990s, Smalley advocated for the need for cheap, clean energy, which he described as the number one problem facing humanity in the 21st century. He described what he called "The Terawatt Challenge", the need to develop a new power source capable of increasing "our energy output by a minimum factor of two, the generally agreed-upon number, certainly by the middle of the century, but preferably well before that."
He also presented a list entitled "Top Ten Problems of Humanity for Next 50 Years". It can be interesting to compare his list, in order of priority, to the Ten Threats formulated by the U.N.s High Level Threat Panel in 2004. Smalleys list, in order of priority, was:
# Energy
# Water
# Food
# Environment
# Poverty
# Terrorism & war
# Disease
# Education
# Democracy
# Population
Smalley regarded several problems as interlinked: the lack of people entering the fields of science and engineering, the need for an alternative to fossil fuels, and the need to address global warming.  He felt that improved science education was essential, and strove to encourage young students to consider careers in science.  His slogan for this effort was "Be a scientist, save the world."
Smalley was a leading advocate of the National Nanotechnology Initiative in 2003.  Suffering from hair loss and weakness as a result of his chemotherapy treatments, Smalley testified before the congressional testimonies, arguing for the potential benefits of nanotechnology in the development of targeted cancer therapies.  Bill 189, the 21st Century Nanotechnology Research and Development Act, was introduced in the Senate on January 16, 2003, by Senator Ron Wyden, passed  the  Senate on November 18, 2003, and at the House of Representatives the next day with a 405–19 vote. President  George  W.  Bush  signed  the  act  into law on December 3, 2003, as Public  Law  108-
153. Smalley was invited to attend.