This issue of Annali dell'Istituto Superiore di Sanità critically evaluates the progression in the ethical relationship between humans and animals (i.e., between biomedical researchers and laboratory animals). The main goal of this publication is in fact to provide a basis for an in-depth discussion of highly debated topics in the contemporary bioethics of animal experimentation, with particular focus on ethological issues and the question of minimal sample size and its contribution to reducing the number of experimental animals. The ethological issues addressed in this publication cover all behavioural patterns specifically moulded by the phylogenetic and ontogenetical history of a given species, a perspective that is often neglected when discussing the promotion of animal welfare.