He served as a board member for the Charles Lindbergh Fund, which promotes environmentally safe technologies. He lent support to causes such as Amnesty International, the Natural Resources Defense Council, and People for the American Way. He joined the Environmental Air Force, and used his Cheyenne II turboprop plane to take government officials and journalists over areas of environmental damage. In the fall of 1987, 77 actors in Santiago, Chile were threatened with execution by the dictator Augusto Pinochet. Reeve was asked by Ariel Dorfman to help save their lives. Reeve flew to Chile and helped lead a protest march. A cartoon then ran in a newspaper showing him carrying Pinochet by the collar with the caption, "Where will you take him, Superman?" For his heroics, he was awarded the Grand Cross of the Bernardo O'Higgins Order, the highest Chilean distinction for foreigners. He also received the Obie Prize and the Annual Walter Brielh Human Rights Foundation award. Reeve's friend Ron Silver later started the Creative Coalition, an organization designed to teach celebrities how to speak knowledgeably about political issues. Reeve was an early member of the group, along with Susan Sarandon, Alec Baldwin, and Blythe Danner.
Reeve left Kessler feeling inspired by the other patients he had met. Because he was constantly being covered by the media, he decided to use his name to put focus on spinal cord injuries. In 1996, he appeared at the Academy Awards to a long standing ovation and gave a speech about Hollywood's duty to make movies that face the world's most important issues head-on. He also hosted the Paralympics in Atlanta and spoke at the Democratic National Convention. He traveled across the country to make speeches, never needing a teleprompter or a script. For these efforts, he was placed on the cover of TIME on August 26, 1996. In the same year, he narrated the HBO film Without Pity: A Film About Abilities. The film won the Emmy Award for "Outstanding Informational Special." He then acted in a small role in the film A Step Towards Tomorrow.
Reeve was elected Chairman of the American Paralysis Association and Vice Chairman of the National Organization on Disability. He co-founded the Reeve-Irvine Research Center, which is now one of the leading spinal cord research centers in the world. He created the Christopher Reeve Foundation (currently known as the Christopher and Dana Reeve Foundation) to speed up research through funding, and to use grants to improve the quality of the lives of people with disabilities. The Foundation to date has given more than $65 million for research, and more than $8.5 million in quality-of-life grants. The Foundation has funded a new technology called "Locomotor Training" that uses a treadmill to mimic the movements of walking to help develop neural connections, in effect re-teaching the spinal cord how to send signals to the legs to walk. This technology has helped several paralyzed patients walk again. Of Christopher Reeve, UC Irvine said, "in the years following his injury, Christopher did more to promote research on spinal cord injury and other neurological disorders than any other person before or since."
In 1997, Reeve made his directorial debut with the HBO film In the Gloaming with Robert Sean Leonard, Glenn Close, Whoopi Goldberg, Bridget Fonda and David Strathairn. The film won four Cable Ace Awards and was nominated for five Emmy Awards including "Outstanding Director for a Miniseries or Special." Dana Reeve said, "There's such a difference in his outlook, his health, his overall sense of well-being when he's working at what he loves, which is creative work." In 1998, Reeve produced and starred in Rear Window, a remake of Alfred Hitchcock's 1954 film. He was nominated for a Golden Globe and won a Screen Actors Guild Award for his performance. On April 25, 1998, Random House published Reeve's autobiography, Still Me. The book spent eleven weeks on the New York Times Best Seller list and Reeve won a Grammy Award for Best Spoken Word Album.
Throughout this time, Reeve kept his body as physically strong as possible by using specialized exercise machines. He did this both because he believed that the nervous system could be regenerated through intense physical therapy, and because he wanted his body to be strong enough to support itself if a cure was found. In 2000, he began to regain some motor function, and was able to sense hot and cold temperatures on his body. His doctor, John McDonald of Washington University in St. Louis, asked him if anything was new with his recovery. Reeve then moved his left index finger on command. "I don't think Dr. McDonald would have been more surprised if I had just walked on water," said Reeve in an interview. Also during that year, he made guest appearances on the long-running PBS series Sesame Street.
In 2001, Reeve was elected to serve on the board of directors for the company TechHealth, headquartered in Tampa, Florida, which provided products and services for severely injured patients. While serving on the TechHealth board, Reeve participated in board meetings and advised the company on strategic direction. He refused compensation. He made phone calls to the company's catastrophically injured patients to cheer them up. Reeve served on TechHealth's board until his death in 2004. After his death, Dana Reeve took his board seat with TechHealth until her death in March 2006.
In 2002, the Christopher and Dana Reeve Paralysis Resource Center, a federal government facility created through a Centers for Disease Control and Prevention non-compete grant, was opened in Short Hills, New Jersey. Its mission is to teach paralyzed people to live more independently. Reeve said, "When somebody is first injured or as a disease progresses into paralysis, people don't know where to turn. Dana and I wanted a facility that could give support and information to people. With this new Center, we're off to an amazing start."
Reeve discussing stem cell research at a conference at MIT, March 2, 2003.
Reeve lobbied for expanded federal funding on embryonic stem cell research to include all embryonic stem cell lines in existence and for open-ended scientific inquiry of the research by self-governance. President George W. Bush limited the federal funding to research only on human embryonic stem cell lines created on or before August 9, 2001, the day he announced his policy, and allotted approximately $100 million for it. Reeve initially called this "a step in the right direction," admitting that he did not know about the existing lines and would look into them further. He fought against the limit when scientists revealed that most of the old lines were contaminated by an early research technique that involved mixing the human stem cells with mouse cells. In 2002, Reeve lobbied for the Human Cloning Prohibition Act of 2001, which would allow somatic cell nuclear transfer research, but would ban reproductive cloning. He argued that stem cell implantation is unsafe unless the stem cells contain the patient's own DNA, and that because somatic cell nuclear transfer is done without fertilizing an egg, it can be fully regulated. In June 2004, Reeve provided a videotaped message on behalf of the Genetics Policy Institute to the delegates of the United Nations in defense of somatic cell nuclear transfer, which was under consideration to be banned by world treaty. In the final days of his life, Reeve urged California voters to vote yes on Proposition 71, which would establish the California Institute for Regenerative Medicine, and allot $3 billion of state funds to stem cell research. Proposition 71 was approved less than one month after Reeve's death.