The Prop 65 list contains a wide range of naturally occurring and synthetic chemicals that are known to California to cause cancer or birth defects or other reproductive harm. They may be additives or ingredients in pesticides, common household products, food, drugs, dyes or solvents. They may be used in manufacturing and construction, or be the byproducts of chemical processes. Proposition 65 requires that the Governor of California maintain and publish a list of these harmful chemicals, and update it annually.

According to the state of California:

A chemical is listed if it has been classified as a reproductive toxicant or carcinogen by an "authoritative" organization on the subject. The U.S. Environmental Protection Agency, U.S. Food and Drug Administration, National Institute for Occupational Safety and Health, the National Toxicology Program, and the International Agency for Research on Cancer are considered authoritative for carcinogens. For reproductive toxicants, appropriate authorities include the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, National Institute for Occupational Safety and Health, and International Agency for Research on Cancer. Chemicals will also be listed if they are required to be labeled or identified as a carcinogen or as a reproductive toxicant by an agency of the state or federal government.