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Cephalopods have been defined as "advanced invertebrates" due to the complexity of their nervous system and to their sophisticated behavioural repertoire. However, until recently, the protection and welfare of this class of invertebrates has been mostly disregarded by EU regulations on the use of laboratory animals. The inclusion of "live cephalopods" in the Directive 2010/63/EU has been prompted by new scientific knowledge on the "sentience" of animals used for experimental or other scientific purposes, a fundamental criterion to which animal species are included or not under the protective umbrella of the Directive. In this scenario, the imminent publication of the Guidelines for the care and welfare of cephalopods in research as an initiative by the CephRes-FELASA-Boyd Group is a sign of ethical progress in the consideration of animals in research, and is likely to have a significant impact on both scientific and practical aspects of research conducted with these animals.