Cognitive deficits following insults to the central nervous system-particularly those involving the hippocampus and related structures-are often persistent and severely debilitating. Progress has been made in establishing the role of the hippocampus in integrating information in the formation of memory necessary for subsequent recollection of information. The present article will review anatomic, physiological, and functional aspects of the hippocampus in reference to learning and memory. Both animal and human hippocampal pathophysiological processes will be explored. Adaptive and maladaptive central nervous system responses will be reviewed, with a special emphasis on neurogenesis. Ideally, physiological and cellular compensatory responses ought to parallel clinical observation. However, this association is not clearly established. Finally, the current understanding of neuromodulatory mechanisms (although quite preliminary) will also be discussed.