If the hippocampus is damaged by disease or injury, it can influence a person's memories as well as their ability to form new memories. Hippocampus damage can particularly affect spatial memory, or the ability to remember directions, locations, and orientations. Because the hippocampus plays such an important role in the formation of new memories, damage to this part of the brain can have a serious long-term impact on certain types of memory. Damage to the hippocampus has been observed upon post-mortem analysis of the brains of individuals with amnesia. Such damage is linked to problems with forming explicit memories such as names, dates, and events.

The exact impact of damage can vary depending on which hippocampus has been affected. Research on mice suggests that damage to the left hippocampus has an effect on the recall of verbal information while damage to the right hippocampus results in problems with visual information. There are a few different factors that can affect the function of the hippocampus.

Age can also have a major impact on the functioning of the hippocampus. MRI scans of human brains have found that the human hippocampus shrinks by around 13% between the ages of 30 and 80. Those who experience such a loss may show significant declines in memory performance. Cell degeneration in the hippocampus has also been linked to the onset of Alzheimer’s disease.

The hippocampus may also play a role in contributing to the development of addictions. Because drugs and alcohol affect the brain's reward systems, the hippocampus creates memories of these satisfying experiences. It also may help form memories of environmental cues associated with substance use that can contribute to intense cravings when these cues are encountered again.