Working alone as well as with Hitchings and Black, Elion developed a multitude of new drugs, using innovative research methods that would later lead to the development of the AIDS drug AZT. She developed the first immunosuppressive drug, azathioprine, used for organ transplants. She also developed the first successful antiviral drug, acyclovir (ACV), for the treatment of Herpes infection.
Elion had also worked for the National Cancer Institute, American Association for Cancer Research and World Health Organization, among other organizations. From 1967 to 1983, she was the Head of the Department of Experimental Therapy for Burroughs Wellcome.
She was affiliated with Duke University as Adjunct Professor of Pharmacology and of Experimental Medicine from 1971 to 1983 and Research Professor from 1983 to 1999.
Rather than relying on trial-and-error, Elion and Hitchings used the differences in biochemistry between normal human cells and pathogens (disease-causing agents such as cancer cells, protozoa, bacteria, and viruses) to design drugs that could kill or inhibit the reproduction of particular pathogens without harming the host cells. The drugs they developed are used to treat a variety of maladies, such as leukemia, malaria, organ transplant rejection (azathioprine), as well as herpes (acyclovir, which was the first selective and effective drug of its kind).