Background: An extremely high percentage of children worldwide are exposed to stress from the first months of life. The aim of this review is to bring together the experimental results related to chronic early-life stress in both human and experimental models. Methods: We aimed to achieve our objective via a thorough review of the literature. Results: Early-life stress is a challenge for the developing organism and leads to negative effects in the medium and long term. The emotional, cognitive, and behavioral domains are compromised due to alterations produced in the nervous system, with some of the most important being related to the main neurotransmission systems. Conclusions: By using experimental models, it is possible to address the study of the structural and functional changes resulting from early-life stress and, thus, plan intervention and prevention alternatives.