Cognitive flexibility, an essential executive function, allows adaptation to environmental changes and represents a fundamental pillar of executive function in neuropsychological models. Based on neurobiological advances and clinical observations, it has emerged as a promising transdiagnostic marker for several psychiatric pathologies, including mood disorders, schizophrenia, and autism spectrum disorders. This review examines the specific role of cognitive flexibility among other cognitive functions, explores potential therapeutic approaches, and presents its evaluation in human and animal models as part of PEPR PROPSY. As the chapters unfold, readers will deepen their understanding of cognitive flexibility while discovering promising avenues for both assessment methods and intervention strategies.