Federal law and policy on laboratory animal care and use governed by the Public Health Service (PHS) and by the National Institutes of Health (NIH), Department of Health and Human Services in the United States is different from the Federal Laws and Regulations of the Animal Welfare Act supervised by the Animal and Plant Health Inspection Service of the United States Department of Agriculture. Early in 1961, the NIH released the first version of the Guide for Laboratory Animal Facilities and Care. With a series of important revisions implemented from 1960 s to 1990 s, the PHS/ NIH have established two comprehensible systems: the IACUC and the Guide for the Care and Use of Laboratory Animals. The NIH office of Laboratory Animal Welfare is responsible for the general administration and coordination of the PHS-governed federal law and policy system and revises and releases the IACUC handbook, and the Guide for the Care and Use of Laboratory Animals in the United States. Both publications are also widely adopted as administration references in the field of international biomedical research. This review describes the historic evolution of PHS/ NIH Law and Policy on the use of laboratory animals.