The history of animal testing can be traced back to the ancient Greeks and Romans, but it transitioned from relatively uncommon to mainstream during the 18th and 19th Centuries. People began pushing for regulations of animal testing practices in Great Britain and the United States in the 1800s.

This public awareness and advocacy grew out of a variety of social forces in Europe. One of those was late 18th Century arguments about the moral significance of animal suffering by Jeremy Bentham, an English jurist, philosopher, and legal and social reformer. Another factor in the public awareness of animal testing was the impact of Charles Darwin's On the Origin of Species, which challenged the view that humans were at the center of the universe. Society's elite began to worry about cruel animal testing. In the late 1800s, animal research controls were passing in Great Britain, but several attempts to pass similar animal testing legislation in the United States failed.

By the end of World War I, animal testing issues were gaining much less attention. Most humane organizations moved into a phase of simply promoting humane education and enforcing animal cruelty laws. The American Society for the Prevention of Cruelty to Animals (ASPCA) abandoned its opposition to animal testing and gave what could be considered a vote of confidence in the medical profession's concern and care for animals.

In the 1950s, organizations like the Animal Welfare Institute and The Humane Society of the United States were founded to devote attention to animal testing. Finally, in 1966, the United States Congress passed the Laboratory Animal Welfare Act, which regulated only the acquisition and handling of animals by dealers. In 1970, Congress amended this act to include the care of animals in research institutions.

Throughout the second half of the 20th century, advocates continued to pressure federal and state governments to pass stricter laws regarding animal testing. Some states stopped allowing the release of pound animals to research facilities. In 1985, Congress passed new animal testing legislation. A new bill required the National Institutes of Health to upgrade its animal testing oversight. Congress also updated the Animal Welfare Act to require more in-house scrutiny of proposals for the use of laboratory animals and more attention to the reduction of pain and distress in animal testing.

Legislative battles continue over the mandated release of shelter animals to laboratories, product safety testing, protection of research facilities against break-ins and vandalism, treatment of nonhuman primates, whether animal testing should be covered under state animal cruelty laws, and student rights regarding dissection and animal experimentation.