The internationally significant 3Rs principle for the protection of animals in research was coined by William Russell and Rex Burch in their 1959 paper "The Principles of Human Experimental Technique". The three "R" stand for "Replacement", "Reduction" and "Refinement". The aim of the 3Rs principle is to replace animal testing with other methods or procedures (Replacement), to reduce unavoidable pain, suffering and harm and the number of laboratory animals to a necessary minimum (Reduction) and to refine interventions and treatments (Refinement).

The 3Rs principle has become the common reference point for a wide range of organizations and initiatives that seek to avoid animal testing or to improve the conditions for laboratory animals. The 3Rs principle has found its way into the legislation of many EU countries through Directive 2010/63/EU on the protection of animals used for scientific purposes, Article 4 of which requires Member States to adhere to the "principle of replacement, reduction and refinement". With its abbreviation "Bf3R", the German Center for the Protection of Laboratory Animals (Deutsches Zentrum zum Schutz von Versuchstieren), newly founded in 2015, refers both to the 3Rs principle and to the Federal Institute for Risk Assessment (BfR). The Bf3R is an integral element of the BfR and supports it through advisory activities for the protection of laboratory animals. The European counterpart to Bf3R is the European Union Reference Laboratory for Alternatives to Animal Testing (EURL-ECVAM), which is located at the Joint Research Centre (JCR) of the European Commission. The EURL-ECVAM also defines alternative methods to animal testing as those that enforce the 3Rs principle: An experimental procedure therefore represents an alternative to animal testing precisely when it is suitable for replacing experiments on animals, reducing their number or refining them in terms of the suffering they cause.

In 2005, the European Commission entered into a partnership with companies from a range of industrial sectors with the aim of developing alternative methods to animal testing (European Partnership to Promote Alternative Approaches to Animal Testing (EPAA)). The founding document of the EPAA is the so-called "3Rs Declaration". Since 2013, the EPAA has been awarding 3Rs prizes every two years for special merits in the development of alternative methods.