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Simple Summary: Small ruminants such as sheep and goats have been increasingly used as animal models due to their dimensions, physiology and anatomy identical to those of humans. Their low costs, ease of accommodation, great longevity and easy handling make them advantageous animals to be used in a wide range of research work. Although there is already a lot of scientific literature describing these species, their use still lacks some standardization. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models for scientific research. Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions, larger than conventional laboratory animals, but very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with a focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research. [ABSTRACT FROM AUTHOR]