Animal models have long been central to neuroscience, providing direct experimental access to neural processes underlying perception, action, cognition, and disease. Over the past century, work in non-human primates (NHPs), rodents, and other species has established key principles of neural organization and behavior and has supported much of translational neuroscience. However, the institutional and material conditions that sustain animal-based research are now changing in fundamental ways. Ethical and regulatory requirements have intensified, costs and approval timelines have increased, and global supply chains, particularly for NHPs, have become fragile. In parallel, advances in human neuroscience, stem-cell-derived systems, and computational approaches have matured to the point that they challenge the historical reliance on animals for many classes of questions. These forces are not eliminating animal research, but they are reshaping the conditions under which it remains feasible, competitive, and scientifically justified. In this Perspective, we examine how these converging pressures are reconfiguring animal-based neuroscience. We review long-term trends in animal use and accessibility, highlighting species-specific constraints and emerging geopolitical asymmetries. We then analyze the growing role of alternative and complementary platforms, including human brain organoids, genetically engineered rodents, small primates, and ‘human-centric’ neurophysiological and imaging approaches, emphasizing both their strengths and limitations. Finally, we discuss the implications of this diversification for research planning, training, and scientific organization. We argue that the future of neuroscience will be defined not by the disappearance of animal models, but by their integration into hybrid experimental frameworks that preserve mechanistic rigor while adapting to evolving scientific and societal constraints.

Keywords: animal models; neuroscience methodology; alternative experimental platforms; translational validity; research ethics and regulation.