The review discusses the role of the hippocampus in pattern separation, a critical process for episodic memory. It highlights evidence from electrophysiological recordings, lesion studies, immediate early gene imaging, transgenic mouse models, and human functional neuroimaging. The dentate gyrus (DG) and CA3 subfields of the hippocampus are identified as key regions involved in pattern separation. The DG is particularly important for pattern separation, while CA3 is involved in pattern completion. Aging and adult neurogenesis impact these processes, with aging leading to pattern separation deficits and neurogenesis potentially facilitating pattern separation. The review also addresses challenges in linking findings across species and approaches, emphasizing the need for further research to understand the regulatory mechanisms of pattern separation.The review discusses the role of the hippocampus in pattern separation, a critical process for episodic memory. It highlights evidence from electrophysiological recordings, lesion studies, immediate early gene imaging, transgenic mouse models, and human functional neuroimaging. The dentate gyrus (DG) and CA3 subfields of the hippocampus are identified as key regions involved in pattern separation. The DG is particularly important for pattern separation, while CA3 is involved in pattern completion. Aging and adult neurogenesis impact these processes, with aging leading to pattern separation deficits and neurogenesis potentially facilitating pattern separation. The review also addresses challenges in linking findings across species and approaches, emphasizing the need for further research to understand the regulatory mechanisms of pattern separation.